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Parathyroid Scintigraphy
A Technologists Guide
European Association of Nuclear Medici
ne
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Contributors
Nish Fernando
Chie Technologist
Department o Nuclear Medicine
St. Bartholomews Hospital, London, UK
Dr. Eli Hindi, MD, PhD
Service de Mdecine NuclaireHpital Saint-Antoine, Paris, France
Sue Huggett
Senior University Teacher
Department o Radiography
City University, London, United Kingdom
Jos Pires Jorge
Proesseur HES-S2
Ecole Cantonale Vaudoise de Techniciens enRadiologie Mdicale (TRM)
Lausanne, Switzerland
Regis Lecoultre
Proesseur HES-S2
Ecole Cantonale Vaudoise de Techniciens en
Radiologie Mdicale (TRM)
Lausanne, Switzerland
Sylviane Prvot
Chair, EANM Technologist Committee
Chie Technologist
Service de Mdecine Nuclaire
Centre Georges-Franois Leclerc, Dijon, France
Domenico Rubello*, MDDirector
Nuclear Medicine Service - PET Unit
S. Maria della Misericordia Hospital
Istituto Oncologico Veneto (IOV), Rovigo, Italy
Audrey Taylor
Chie Technologist
Department o Nuclear Medicine
Guys and St. Thomas Hospital, London, UK
Linda Tutty
Senior Radiographer
St. Jamess Hospital
Dublin, Ireland
* Domenico Rubello, MD
is coordinator of the National Study Group on parathyroid scintigraphy of AIMN (Italian Association of Nuclear
Medicine) and is responsible for developing study programmes on minimally invasive radioguided surgery in patients
with hyperparathyroidism for GISCRIS (Italian Study Group on Radioguided Surgery and Immunoscintigraphy)
Acknowledgement for the photo:
P. Lind, Department of Nuclear Medicine, LKH Klagenfurt, Austria
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Contents
Foreword 4
Sylviane Prvot
Introduction 5
Sue Huggett
Chapter 1 Applications o parathyroid imaging 612
Eli Hindi
Chapter 2 Radiopharmaceuticals 1317
Linda Tutty
Chapter 3 Imaging equipment preparation and use 1823
Jos Pires Jorge and Regis Lecoultre
Chapter 4 Patient preparation 2428
Audrey Taylor and Nish Fernando
Chapter 5 Imaging protocols 2932
Nish Fernando and Sue Huggett
Chapter 6 Technical aspects o probe-guided surgery or parathyroid adenomas 3339
Domenico Rubello
Reerences 4043
This booklet was sponsored by an educational grant from Bristol-Myers Squibb Medical Imaging.
The views expressed are those of the authors and not necessarily of Bristol-Myers Squibb Medical
Imaging.
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ForewordSylviane Prvot
Today the notion o competence is at the
heart o proessional development. Technol-
ogists specic proessional skills o working
eciently and knowledgeably are essential
to ensure high-quality practice in nuclear
medicine departments.
Since they were ormed, the EANM Tech-
nologist Committee and Sub-committee onEducation have devoted themselves to the
improvement o nuclear medicine technolo-
gists (NMTs) proessional skills.
Publications that will assist in the setting o
high standards or NMTs work throughout
Europe have been developed. A series o bro-
chures, technologists guides, was planned in
early 2004. The rst o these was dedicated tomyocardial perusion imaging and the current
volume, the second in the planned series, ad-
dresses parathyroid imaging.
Renowned authors with expertise in the eld
have been selected to provide an inormative
and truly comprehensive tool or technolo-
gists that will serve as a reerence and improve
the quality o daily practice.
I am grateul or the hard work o all the con-
tributors, who have played a key role in ensur-
ing the high scientic content and educational
value o this booklet. Many thanks are due to
Sue Huggett, who coordinated the project,
to the members o the EANM Technologist
Sub-committee on Education and particularly
to Bristol-Myers Squibb Imaging or their con-
dence and generous sponsorship.
Eorts to image the parathyroid gland date
back many years. I hope this brochure will be
useul to technologists in the management
o patients with hyperparathyroidism and will
benet these patients by optimising care and
welare.
Sylviane Prvot
Chair, EANM Technologist Committee
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IntroductionSue Huggett
The rst publication o the EANM Technolo-
gist Committee sponsored by Bristol Myers
Squibb in 2004 was a book on myocardial
perusion imaging or technologists. We
are very grateul that they have sponsored
us again this year to produce this book on
parathyroid imaging, the second book in
what we hope will be a series.
We hope that we have combined the theory
and rationale o imaging with the practicalities
o patient care and equipment use. I think that
certain things I wrote or the last book bear re-
peating, and so I will do so here or the benet
o those or whom this is their rst book.
Knowledge o imaging theory provides a deeper
understanding o the techniques that is satisy-ing or the technologist and can orm the basis
or wise decision making. It also allows the tech-
nologist to communicate accurate inormation
to patients, their carers and other sta. Patient
care is always paramount, and being able to
explain why certain oods must be avoided or
why it is necessary to lie in awkward positions
improves compliance as well as satisaction.
Awareness o the rationales or using certain
strategies is needed in order to know when
and how various protocol variations should be
applied, in acquisition or analysis, e.g. or the
patient who cannot lie fat or long enough
or subtraction and may need to be imaged
with another protocol or when we may need
a dierent lter i the total counts are low.
Protocols will vary between departments,
even within the broader terms o the EANM
Guidelines. This booklet is not meant to sup-
plant these protocols but will hopeully sup-
plement and explain the rationales behind
them, thereby leading to more thoughtul
working practices.
The authors are indebted to a number osources or inormation, not least local proto-
cols, and reerences have been given where
original authors are identiable. We apolo-
gise i we have inadvertently used material
or which credit should have been, but was
not, given.
We hope that this booklet will provide help-
ul inormation as and when it is needed sothat the integration o theory and practice is
enabled and encouraged.
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Applications o parathyroid imagingEli Hindi
Primary hyperparathyroidism
Primary hyperparathyroidism (pHPT) is a
surgically correctable disease with the third
highest incidence o all endocrine disorders
ater diabetes mellitus and hyperthyroidism
(Al Zahrani and Levine 1997). Through their
secretion o parathyroid hormone (PTH), the
two pairs o parathyroid glands, located in the
neck posterior to the thyroid gland, regulateserum calcium concentration and bone me-
tabolism. PTH promotes the release o calcium
rom bone, increases absorption o calcium
rom the intestine and increases reabsorp-
tion o calcium in the renal tubules. In turn,
the serum calcium concentration regulates
PTH secretion, a mechanism mediated via a
calcium-sensing receptor on the surace o
the parathyroid cells. pHPT is caused by thesecretion o excessive amounts o PTH by
one or more enlarged diseased parathyroid
gland(s). Patients with pHPT may suer rom
renal stones, osteoporosis, gastro-intestinal
symptoms, cardiovascular disease, muscle
weakness and atigue, and neuropsychologi-
cal disorders. The highest prevalence o the
disease is ound in post-menopausal women.
A prevalence o 2% was ound by screening
post-menopausal women (Lundgren).
In the past, pHPT was characterised by severe
skeletal and renal complications and apparent
mortality. This may still be the case in some
developing countries. The introduction o
calcium auto-analysers in the early 1970s
led to changes in the incidence o pHPT and
deeply modied the clinical spectrum o the
disease at diagnosis (Heath et al. 1980). Most
new cases are now biologically mild without
overt symptoms (Al Zahrani and Levine 1997).
Parathyroidectomy is the only curative treat-
ment or pHPT. In the recent guidelines o the
US National Institute o Health (NIH), surgery
is recommended or all young individuals and
or all patients with overt symptoms (Bilezikianet al. 2002). For patients who are asymptom-
atic and are 50 years old or older, surgery is
recommended i any o the ollowing signs
are present: serum calcium greater than 10
mg/l above the upper limits o normal; 24-h
total urine calcium excretion o more than 400
mg; reduction in creatinine clearance by more
than 30% compared with age-matched per-
sons; bone density more than 2.5 SDs belowpeak bone mass: T score < -2.5. Surgery is also
recommended when medical surveillance
is either not desirable or not possible. Ater
complete baseline evaluation, patients who
are not operated on need to be monitored
twice yearly or serum calcium concentration
and yearly or creatinine concentration; it is
also recommended that bone mass measure-
ments are obtained on a yearly basis (Bilezikian
et al. 2002). Some authors recommend para-
thyroidectomy or all patients with a secure
diagnosis o pHPT (Utiger 1999).
Successul parathyroidectomy depends on
recognition and excision o all hyperunc-
tioning parathyroid glands. pHPT is typically
caused by a solitary parathyroid adenoma, less
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Chapter 1: Applications of parathyroid imaging
requently (about 15% o cases) by multiple
parathyroid gland disease (MGD) and rarely
(about 1% o cases) by parathyroid carcino-
ma. Patients with MGD have either double
adenomas or hyperplasia o three or all our
parathyroid glands. Most cases o MGD are
sporadic, while a small number are associated
with hereditary disorders such as multiple en-
docrine neoplasia type 1 or type 2a or amilialhyperparathyroidism (Marx et al. 2002). Con-
ventional surgery consists in routine bilateral
exploration with identication o all our para-
thyroid glands.
Imaging is mandatory beore reoperation
For several decades, preoperative imaging was
not used beore rst-time surgery. Unguided
bilateral exploration, dissecting all potentialsites in the neck, achieved cure in 9095% o
patients (Russell and Edis 1982). The two main
reasons or ailed surgery are ectopic glands
(retro-oesophageal, mediastinal, intrathyroid,
in the sheath o the carotid artery, or unde-
scended) and undetected MGD (Levin and
Clark 1989). Repeat surgery is associated with a
dramatic reduction in the success rate and an
increase in surgical complications. Imaging is
thereore mandatory beore reoperation (Sosa
et al. 1998). 99mTc-sestamibi scanning (Coakley
et al. 1989) has been established as the imag-
ing method o choice in reoperation o persis-
tent or recurrent hyperparathyroidism (Weber
et al. 1993). In these patients it is necessary to
have all inormation concerning the rst inter-
vention, including the number and location o
parathyroid glands that have been seen by the
surgeon and the size and histology o resected
glands. Whichever 99mTc-sestamibi scanning
protocol is used, it is necessary to provide the
surgeon with the best anatomical inormation
by using both anterior and lateral (or oblique)
views o the neck, and SPECT whenever use-
ul, especially or a mediastinal ocus. It is the
authors opinion that99m
Tc-sestamibi resultsshould be conrmed with a second imaging
technique (usually ultrasound or a neck ocus
and CT or MRI or a mediastinal image) beore
proceeding to reoperation.
Scanning with 99mTc-sestamibi is increasingly
ordered on a routine basis or rst-time
parathyroidectomy
The rst exploration is the best time to curehyperparathyroidism. Most surgeons would
now appreciate having inormation concern-
ing whereabouts in the neck to start dissec-
tion and the possibility o ectopic parathyroid
glands (Sosa et al. 1998; Liu et al. 2005). When
the rare cases (2-5%) o ectopic parathyroid
tumours are recognised preoperatively, the
success o bilateral surgery can now reach
very close to 100% (Hindi et al. 1997). In the
case o a mediastinal gland, the surgeon can
proceed directly with rst-intention thoracos-
copy, avoiding unnecessary initial extensive
neck surgery in the search or the elusive
gland (Liu et al. 2005). Preoperative imaging
would also shorten the duration o bilateral
surgery (Hindi et al. 1997). By allowing the
surgeon to nd the oending gland earlier in
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the operation, the time necessary or rozen
section examination can be used by the sur-
geon or inspection o the other parathyroid
glands, also reducing surgeon anxiety.
Important points to know when proceeding
with parathyroid imaging
Imaging is not or diagnosis. The increase
in plasma levels o calcium (normal value88105 mg/l) and PTH (normal value 1058
ng/l) establishes the diagnosis.
Imaging does not identiy normal parathy-
roid glands, which are too small (2050 mg)
to be seen.
Imaging should detect abnormal para-
thyroid(s) and indicate the approximate sizeand the precise relationship to the thyroid
(the level o the thyroid at which the para-
thyroid lesion is seen on the anterior view;
and whether it is proximal to the thyroid or
deeper in the neck on the lateral or oblique
view or SPECT) (Fig. 1).
Imaging should identiy ectopic glands (add
SPECT in cases o a mediastinal ocus, and
ask or additional CT or MRI or conrmation
and anatomical landmarks) (Fig. 2).
Imaging should be able to dierentiate pa-
tients with a single adenoma rom those
with MGD (Fig. 3).
Imaging should identiy thyroid nodules
that may require concurrent surgical re-
section.
The choice o imaging technique
The most common preoperative localisation
methods are radionuclide scintigraphy and
ultrasound. As stated beore, the two main
reasons or ailed surgery are ectopic glands
and undetected MGD (Levin and Clark 1989).Because high-resolution ultrasound would,
even in skilled hands, ail to detect the major-
ity o these cases, it is not optimal or preop-
erative imaging as a single technique. In the
study by Haber et al. (2002), ultrasound missed
six o eight ectopic glands and ve o six cases
o MGD. Ultrasound may, however, be useul
in combination with 99mTc-sestamibi imaging
(Rubello et al. 2003).
99mTc-sestamibi scanning is now considered
the most sensitive imaging technique in pa-
tients with pHPT (Giordano et al. 2001; Mullan
2004). Whatever the protocol used, 99mTc-ses-
tamibi scanning will usually meet the require-
ment o detecting ectopic glands (all eight
were detected in the study by Haber et al.).
With regard to the recognition o MGD, how-
ever, the protocol in use will determine the
sensitivity. When 99mTc-sestamibi is used as a
single tracer with planar imaging at two time
points -- the dual-phase (or washout) method
the sensitivity or primary hyperplasia is very
low (Tailleer et al. 1992; Martin et al. 1996). Bet-
ter results can be obtained by adding SPECT.
Subtraction scanning, using either
123
I (Borley
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Chapter 1: Applications of parathyroid imaging
et al. 1996; Hindi et al. 2000; Mullan 200)
or 99mTc-pertechnetate (Rubello et al. 2003)
in addition to 99mTc-sestamibi, improves the
sensitivity or hyperplastic glands. One di-
culty with subtraction imaging is keeping the
patient still or the time necessary to scan the
thyroid, to inject 99mTc-sestamibi and to record
images o this second tracer. Simultaneous
recording o123
I and99m
Tc-sestamibi can be asimple answer to these diculties. It prevents
arteacts on subtraction images due to pa-
tient motion, and shortens the imaging time
(Hindi et al. 1998; Mullan 2004).
Preoperative imaging has opened a new era
o minimally invasive parathyroid surgery
Conventional bilateral exploration is still
considered the gold standard in parathyroidsurgery. However, the introduction o99mTc-
sestamibi scanning, the availability o intra-
operative adjuncts such as the gamma probe
and intraoperative monitoring o PTH to help
detect MGD have challenged the dogma o
routine bilateral exploration. When preopera-
tive imaging points to a single well-dened
ocus, unequivocally suggesting a solitary
adenoma, the surgeon may now choose o-
cussed surgery instead o bilateral exploration.
Focussed excision can be made by open sur-
gery through a mini-incision, possibly under
local anaesthesia, or by video-assisted endo-
scopic surgery under general anaesthesia (Lee
and Inabnet 2005). Compared with patients
who undergo bilateral surgery, those in whom
ocussed parathyroid surgery is successully
completed enjoy a shorter operation time,
the possibility o local anaesthesia, a better
cosmetic scar, a less painul postoperative
course, less proound postoperative transient
hypocalcaemia and an earlier return to normal
activities. The act that many clinicians now
use a lower threshold or surgery is partly due
to the perception that parathyroid surgery is
easier than in the past (Utiger 1999).
Patients at specic risk o ailure o minimal
surgery are those with unrecognised MGD.
Thereore, when choosing minimal surgery,
the surgeon is committed to distinguishing
cases o MGD either preoperatively, through
an appropriate imaging protocol, or by intra-
operative monitoring o PTH plasma levels, or
by a combination o both. The true sensitivityo intraoperative PTH or MGD is still under
debate. What raises concern is that studies
relying solely on intraoperative measurements
report a low percentage o MGD, only 3% (Mo-
linari et al. 1996), which is three to our times
lower than is generally observed during rou-
tine bilateral surgery. Whether this will lead to
higher rates o late recurrence is not known. It
is thus important that imaging methods used
to select patients or ocussed surgery have a
high sensitivity or detecting MGD.
In this new era o ocussed operations, the
success o parathyroid surgery depends not
only on an experienced surgeon but also on
excellent interpretation o images. A localisa-
tion study with high accuracy is mandatory to
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10
avoid conversion o the surgery to a bilateral
exploration under general anaesthesia ater
minimal surgery has been started. It is impor-
tant to avoid conusion with a thyroid nod-
ule, and precise anatomical description is also
important. With enlargement and increased
density, superior parathyroid adenomas can
become pendulous and descend posteriorly.
A lateral view (or an oblique view or SPECT)should indicate whether the adenoma is close
to the thyroid or deeper in the neck (tracheo-
oesophageal groove or retro-oesophageal).
This inormation is useul, because visualisa-
tion through the small incision is restricted.
Moreover, the surgeon may choose a lateral
approach to excise this gland instead o an
anterior approach. To achieve a high sensitiv-
ity in detecting MGD with subtraction tech-niques, the degree o subtraction should be
monitored careully. Progressive incremental
subtraction with real-time display is a good
way to choose the optimal level o subtraction
(residual 99mTc-sestamibi activity in the thyroid
area should not be lower than in surround-
ing neck tissues). Oversubtraction could easily
delete additional oci o activity and in some
patients provide a alse image suggestive o
a single adenoma.
Secondary hyperparathyroidism
Secondary hyperparathyroidism is a common
complication in patients with chronic renal
ailure. Hypocalcaemia, accumulation o phos-
phate and a decrease in the active orm o
vitamin D lead to increased secretion o PTH.
With chronic stimulation, hyperplasia o para-
thyroid glands accelerates and may develop
into autonomous adenomas. The extent o
parathyroid growth then becomes a major
determinant o PTH hypersecretion. Second-
ary hyperparathyroidism leads to renal bone
disease, the development o sot tissue calci-
cations, vascular calcications and increased
cardiovascular risk, among other complica-tions. When medical therapy ails, surgery
becomes necessary. Surgery can be either
subtotal parathyroidectomy, with resection
o three glands and partial resection o the
ourth gland, or total resection with grating
o some parathyroid tissue into the sot tissues
o the orearm in order to avoid permanent
hypoparathyroidism.
Preoperative imaging
Surgery o secondary hyperparathyroidism
requires routine bilateral identication o all
parathyroid tissue. Moreover, early studies
based on single-tracer 99mTc-sestamibi scan-
ning have reported a very low sensitivity
o about 050% in detecting hyperplastic
glands. Ineciency o single-tracer techniques
both in secondary hyperparathyroidism and
in primary hyperplasia is possibly due to more
rapid washout o tracer rom hyperplastic
glands than rom parathyroid adenomas. For
those reasons, preoperative imaging has not
yet gained wide acceptance among surgeons.
Dual-tracer subtraction imaging, planar or
SPECT, provides substantial improvement in
the rate o detection o hyperplastic glands in
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Chapter 1: Applications of parathyroid imaging
patients with renal ailure (Hindi et al. 1999;
Peri et al. 2005)
What inormation can be obtained?
The preoperative map may acilitate rec-
ognition o the position o aberrant para-
thyroid glands, also reducing the extent o
dissection (Hindi et al. 1999).
Parathyroid glands with major ectopia
would be missed without preoperative
imaging.
Although the usual number o parathyroid
glands is our, some individuals (about 10%)
have a supernumerary th gland (Aker-
strm et al. 1984). When this inormation is
provided by preoperative imaging, it mayprevent surgical ailure or late recurrence
(Hindi et al. 1999).
Imaging ndings in patients with persistent
or recurrent secondary hyperparathyroidism
Immediate ailure and delayed recurrence are
not unusual, occurring in 1030% o patients.
Imaging is mandatory beore reoperation.
Knowledge o all details concerning the initial
intervention is necessary or interpretation. As
with primary hyperparathyroidism, we recom-
mend that lesions seen on the 99mTc-sestamibi
scan be matched with a second radiological
technique (ultrasound or MRI) or conrmation
and identication o anatomical landmarks
beore reoperation.
Some aspects specic to patients reoperated
or secondary hyperparathyroidism need to
be emphasised:
Specic views o the orearm should be
obtained in patients who have had a para-
thyroid grat.
It is not unusual or imaging in these pa-tients to show two oci o activity, one
corresponding to recurrent disease at the
subtotally resected gland (or grated tissue)
and the other corresponding to an ectopic
or th parathyroid, missed at initial inter-
vention (unpublished data).
Figure 1
Parathyroid subtraction scintigraphy, with simul-
taneous acquisition o99mTc-sestamibi and 123I
in a patient with primary hyperparathyroidism.
The anterior view and the lateral view show a
solitary adenoma located at the lower right pole
o the thyroid. At surgery, an adenoma o 1.9 g
was ound at the predicted site.
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1
Figure 2This patient with a previous history o thyroid surgery (right lobectomy) was reerred with a recent
diagnosis o primary hyperparathyroidism. Ultrasound examination suggested the presence o
a parathyroid adenoma at the side o previous thyroid lobectomy, which was a alse-positive
image. The large eld o view 99mTc-sestamibi acquisition shows a mediastinal ocus (arrow).
The suspected ectopic parathyroid was conrmed by MRI (arrow). A mediastinal parathyroid
adenoma o 0.59 g was resected.
Figure 3
Parathyroid 99mTc-sestamibi/123I subtraction scintigraphy in a patient with primary hyperpara-
thyroidism. The computed subtraction images show two sites o preerential 99mTc-sestamibi
uptake: one at the lower third o the let thyroid lobe and the second lateral to the lower pole
o the right thyroid lobe. Two adenomas were excised: a let parathyroid adenoma weighing
2.3 g and a right adenoma weighing 0.07 g.
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1
RadiopharmaceuticalsLinda Tutty
Radiopharmaceuticals used or
parathyroid scintigraphy
Details o the photo peak energy, hal-lie, e-
ective dose and standard dose or radiophar-
maceuticals commonly used or parathyroid
scintigraphy are shown in Table 1.
201Tl-chloride201
Tl-chloride has a physical hal-lie o 73.1 h.Its main photo peak is due to characteristic x-
rays o mercury, which have an energy range
o 6983 keV. In addition, gamma rays are pro-
duced at 167 keV (8%) and 135 keV (2%). The
administered activity is 80 MBq and it is given
intravenously. 201Tl-chloride is taken up by ab-
normal parathyroid tissue and thyroid tissue in
proportion to blood fow.
99mTc-pertechnetate99mTc-pertechnetate has a hal-lie o 6 h and a
gamma energy o 140 keV. 99mTc-pertechnetate is
used to delineate the thyroid gland because unc-
tioning thyroid parenchyma traps it. This image is
then subtracted rom the 201Tl or 99mTc-sestamibi
images, and what remains is potentially a parathy-
roid adenoma. When utilising 201Tl, the adminis-
tered activity is usually 75150 MBq, depending on
the administered radioactivity o201Tl and which o
the two radiopharmaceuticals is administered rst.
I using 99mTc-sestamibi, the amount o pertechne-
tate administered is usually 185370 MBq, because99mTc-sestamibi has a higher total activity in the
thyroid tissue than 201Tl.
99m
Tc-sestamibiThe range o intravenously administered radio-
activity is 185-900 MBq; the typical dose is 740
MBq. This radiotracer localises in both parathyroid
gland and unctioning thyroid tissue, and usually
washes out o normal thyroid tissue more rap-
idly than out o abnormal parathyroid tissue. The
exact mechanism o uptake remains unknown
(Farley 2004). 99mTc-sestamibi uptake depends on
numerous actors, including perusion, cell cycle
phase and unctional activity (Beggs and Hain2005). The nal cellular localisation o99mTc-sesta-
mibi is within the mitochondria. It accumulates in
the mitochondria o many tissues but particularly
in normal cardiac and thyroid cells; it is especially
prominent in overactive parathyroid glands and
is held there preerentially (Farley 2004).
123I-sodium iodide
123I has a hal-lie o 13 h and emits a photonwith an energy o 159 keV. It has been used
particularly with 99mTc-sestamibi as a thyroid-
imaging agent in subtraction studies. The
administered dose, given orally, ranges rom
7.5 to 20 MBq.
99mTc-tetroosmin99mTc-tetroosmin use in parathyroid imaging
is described in the literature (Smith and Oates
2004). Its manuacturers do not license it or
use as a parathyroid scintigraphy agent. 99mTc-
sestamibi and 99mTc-tetroosmin have similar
imaging characteristics (Smith and Oates
2004). The typical dose o administered activ-
ity is 740 MBq.
11
C-methionine11C-methionine has a hal-lie o 20 min. It is
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1
cyclotron produced. Its uptake reects amino
acid refux into stimulated parathyroid tissue
(Otto et al. 2004; Beggs and Hain 2005). Up-
take in infammatory conditions may pose
a problem and should be considered when
interpreting images. The typical radioactivity
dose ranges between 240 and 820 MBq, with
an average intravenous dose o 400 MBq.
18F-FDG18F-FDG has a hal-lie o 110 min and is cy-
clotron produced. 18F-FDG allows glucose
metabolism to be assessed and evaluated
using PET. There is dierential concentra-
tion o FDG in abnormal parathyroid tissue
and this dierence is used to demonstrate
the abnormal gland. FDG also accumulates
in other malignant and benign tissues, andin infamed or inected tissue; this potentially
limits its useulness. The typical intravenous
dose is 400 MBq.
Radiopharmaceutical eatures
Multiple radiopharmaceuticals have been
described or the detection o parathyroid le-
sions. Thallium, sestamibi and tetroosmin are
the three most commonly used (Ahuja et al.
2004). All these agents were originally devel-
oped or cardiac scanning. In the 1980s, 201Tl
was the most commonly used agent, but it
has a longer hal-lie and delivers a higher ra-
diation dose to the patient (Kettle 2002). Con-
sequently, 201Tl is no longer commonly used,
and most recent literature reers to the use o99m
Tc-sestamibi. However, or the subtraction
method it is probable that each radiopharma-
ceutical would provide the same diagnostic
inormation (Kettle 2002).
Subtraction agents
Thyroid-specic imaging with 123I or 99mTc-
pertechnetate may be employed using a sub-
traction method to dierentiate parathyroid
rom thyroid activity (Clark 2005).
The two main agents used or imaging the
thyroid are 123I (sodium iodide) and 99mTc-
pertechnetate. There is a slight preerence or
the use o123I, as it is organied and thereore
provides a stable image. The pertechnetate
washes out rom the thyroid gland with time,
and i there is some delay in imaging there
may be a reduction in the quality o thethyroid image (Kettle 2002). However, both
agents may be aected i the patient is taking
thyroxine or anti-thyroid medications or has
recently received iodine contrast agents.
Thyroid-specic radiopharmaceuticals may
aid delineation o the thyroid parenchyma i
required ater dual-phase imaging. This may
be helpul as a second-line visual subtraction
procedure when no parathyroid adenoma is
visible on dual-phase parathyroid imaging
(Clark 2005).
Activities given or imaging the thyroid
and parathyroid glands are as ollows: 99mTc
pertechnetate, 80 MBq; 123I, 0 MBq; 201Tl,
80 MBq;
99m
Tc-sestamibi, 900 MBq. I a
99m
Tc-
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Chapter 2: Radiopharmaceuticals
pertechnetate/99mTc-sestamibi combination
is used then the radiation dose or the com-
bined study is 11.6 mSv. I123I and 201Tl are used,
this rises to 18.3 mSv.
Dual-phase agents99mTc-sestamibi and 99mTc-tetroosmin are com-
monly used agents or dual-phase parathyroid
scintigraphy. The washout technique relies onthe act that while 99mTc-sestamibi and 99mTc-tet-
roosmin are taken up by both the thyroid gland
and the parathyroid at a similar rate, there is a
aster rate o washout rom the thyroid gland.
These tracers localise in the thyroid gland as
well as in parathyroid adenomas. This makes
correlation o the adenoma in relation to the
thyroid gland possible on planar as well as earlySPECT imaging. 99mTc-sestamibi is released rom
the thyroid with a hal-lie o about 30 min but
is usually retained by abnormal parathyroid
glands (Smith and Oates 2004). 99mTc-tetroos-
min may clear more slowly rom the thyroid
gland. This dierential washout improves the
target-to-background ratio so that abnormal
parathyroid tissue should be more visible on
delayed images (Smith and Oates 2004; Clark
2005). However, thyroid adenomas and carcino-
mas can coexist and may retain 99mTc-sestamibi
or 99mTc-tetroosmin, resulting in alse positive
results (Smith and Oates 2004).
99mTc-sestamibi and 99mTc-tetroosmin have
comparable imaging characteristics. Usually,
the choice o imaging agent depends on its
availability and the experience o the nuclear
medicine radiologist.
The dual-phase subtraction method with ad-
junctive thyroid-selective imaging (99mTc or 123I)
may be helpul, or even essential, in patients
with goitres or other conounding underly-
ing thyroid disease, ater thyroid surgery or in
those patients with a palpable mass (Smithand Oates 2004).
PET imaging agents
Use o18F-fuorodeoxyglucose (FDG) positron
emission tomography (PET) and 11C- methio-
nine PET or parathyroid imaging has been de-
scribed (Otto et al. 2004; Beggs and Hain 2005).
Initial studies with PET have shown conficting
results when using FDG as a tracer to image theparathyroid glands (Beggs and Hain 2005; Otto
et al. 2004). It has been shown that 11C-methio-
nine PET holds more promise than FDG PET im-
aging o the parathyroid localisation (Beggs and
Hain 2005). 11C-methionine PET scanning is o
value in cases o primary hyperparathyroidism
in which conventional imaging techniques have
ailed to localise the adenoma beore proceed-
ing to surgery, or in patients in whom surgery
has been perormed but has ailed to correct the
hyperparathyroidism (Beggs and Hain 2005).
Adverse reactions to
radiopharmaceuticals
Table 2 shows side-eects and reactions to
radiopharmaceuticals used or parathyroid
scintigraphy.
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1
Table 1
Radiopharmaceuticals used or parathyroid scintigraphy
201Tl- 99mTc 99mTc 11C 18F
chloride sestamibi tetroosmin methionine fuorodeoxy-
glucose
Photo peak 69-80 (98% 140 140 511 511
energy abundance)
(keV) 135 (2%)
167 (8%)Hal-lie 73.1 hours 6 hours 6 hours 20 min 110 min
Cyclotron Always Always Cyclotron Cyclotron
product available available produced produced
to be (24-month (6-month
ordered shel lie at shel lie at
ready or room 2-8C
use temperature)
Eectivedose adult
(mSv)
18 11 9 2 10
Standard 80 900 900 400 400
dose*(MBq)
*Allowable upper limits o radiotracers may dier rom country to country. Please reer to the
Summary o Product Characteristics in each European country. Doses given here are quoted
rom ARSC, December 1998.
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Chapter 2: Radiopharmaceuticals
Table 2
Adverse reactions to radiopharmaceuticals used or parathyroid scintigraphy (as printed in J
Nucl Med 1996;37:185192, 10641067)
Radiopharmaceutical Side-eects, reactions201TI-chloride Fever, erythema, fushing, diuse rash,
pruritis, hypotension99mTc-pertechnetate Chills, nausea, vomiting, diuse rash,
pruritis, hives/urticaria, chest pain,
tightness or heaviness, hypertension,
dizziness, vertigo, headache, diaphoresis,
anaphylaxis
99mTc-sestamibi Nausea, erythema, fushing, diuse rash,
pruritis, seizures, headache, metallic taste,
tingling
123I-Sodium iodide Nausea, vomiting, diuse rash,
pruritus, hives/urticaria, chest pain, tightness
or heaviness, respiratory reaction,tachycardia, syncope or aintness and
headache, tachypnea, parosmia
99mTc-tetroosmin Angina, hypertension, torsades de
pointes (these three probably occurred
because o underlying heart disease);
vomiting, abdominal discomort,
cutaneous allergy, hypotension,
dyspnoea, metallic taste, burning o
mouth, unusual odour, mild leucocytosis
18F-FDG None
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1
Imaging equipment preparation and useJos Pires Jorge and Regis Lecoultre
Quality control procedures that must be
satisactorily perormed beore imaging
Ater acceptance testing, a QC protocol must
be set up in each department and ollowed
in accordance with national guidelines. The
ollowing routine quality control test schedule
is typical:
a) Daily energy peaking
b) Daily food uniormity tests
c) Daily gamma camera sensitivity measure-
ment
d) Weekly linearity and resolution assess-
ment
e) Weekly centre-o-rotation calibration
A routine quality control programme or a
SPECT gamma camera includes quality control
procedures appropriate to planar scintillation
cameras (ad) and specic SPECT quality con-
trols (e). Further, more complex tests should be
undertaken on a less requent basis.
Energy peaking
This quality control procedure consists in
peaking the gamma camera or relevant
energies prior to obtaining food images. It
is mandatory that the energy peaking is un-
dertaken on a daily basis and or each radio-
nuclide used.
Checking the peaking is needed to ascertain
that:
The camera automatic peaking circuitry is
working properly
The shape o the spectrum is correct
The energy peak appears at the correctenergy
There is no accidental contamination o the
gamma camera
It is recommended that the spectra obtained
during peaking tests are recorded.
Daily food uniormity testsAter a successul peaking test it is recom-
mended that a uniormity test is perormed
on a daily basis. Flood elds are acquired and
evaluation o camera uniormity can be made
on a visual assessment. Quantitative param-
eters should also be computed regularly and
recorded in order both to demonstrate sud-
den variations rom normal and to alert the
technologist to progressive deterioration in
the equipment. On cameras that have inter-
changeable uniormity correction maps, it
is vital that one is used that is for the correct
nuclide, accurate and up to date.
Daily gamma camera sensitivity
measurement
A practical means o measuring sensitivity is
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Chapter 3: Imaging equipment - preparation and use
by recording the time needed to acquire the
food eld using the known activity. It should
not vary by more than a ew percent rom one
day to another.
Weekly linearity and resolution assessment
Linearity and resolution should be assessed
weekly. This may be done using transmission
phantoms.
Centre o rotation calibration
The centre o rotation measurement deter-
mines the oset between the axis o rotation
o the camera and the centre o the matrix
used or reconstruction, as these do not cor-
respond automatically.
The calibration o the centre o rotation ismade rom the reconstruction o a tomo-
graphic acquisition o a point source placed
slightly oset rom the mechanical centre o
rotation o the camera. A sinogram is ormed
rom the projections and is used to t the
maximum count locations to a sine wave. De-
viations between the actual and tted curves
should not exceed 0.5 pixels.
Collimator
The choice o a collimator or a given study
is mainly determined by the tracer activity.
This will infuence the statistical noise con-
tent o the projection images and the spatial
resolution. The number o counts needs to be
maximised, possibly at the expense o some
resolution and taking into account that in
parathyroid imaging the dierence in tracer
activity between 99mTcO4 (thyroid only) and
any 99mTc-labelled agent (thyroid and parathy-
roid) must be signicant.
Collimators vary with respect to the relative
length and width o the holes. The longer the
hole length, the better the spatial resolution
obtained, but at the expense o a lower countsensitivity. Conversely, a larger hole gives a
better count sensitivity but with a loss o spa-
tial resolution.
When using 201Tl, the available counts are
greatly reduced owing to the long hal-lie
o the isotope and the consequent limited
dose; so traditionally a low-energy general-
purpose collimator is recommended. With99mTc-pertechnetate and 99mTc-labelled agents,
count rate is no longer a major limitation, and
urthermore, the resolution o a high-resolu-
tion collimator decreases less with distance
rom the source than does that o a general-
purpose collimator. Thus a high-resolution
collimator is currently recommended or
SPECT imaging, despite the lower sensitivity.
Although the choice o collimator is crucial, it
should be borne in mind that other technical
aspects play an important role in determining
optimal spatial resolution, such as the matrix
size, the number o angles and the time per
view.
Matrix and zoom actor
The SPECT images (or projections rom the
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0
angles round the patient) create multiple raw
data sets containing the representation o the
data in one projection. Each o these is stored
in the computer in order to process them later
on and extract the inormation.
Matrix
Each projection is collected into a matrix.
These are characterised by the number opicture elements or pixels. Pixels are square
and organised typically in arrays o 66,
128128 or 256256.
In act, the choice o matrix is dependent on
two actors:
a) The resolution: The choice should not de-
grade the intrinsic resolution o the object. Thecommonly accepted rule or SPECT (Groch
and Erwin 2000) is that the pixel size should be
one-third o the ull-width at hal-maximum
(FWHM) resolution o the organ, which will
depend on its distance rom the camera ace.
The spatial resolution o a SPECT system is o
the order o 1825 mm at the centre o rota-
tion (De Puey et al. 2001). Thus a pixel size o
6-8 mm is sucient, which, or a typical large
eld o view camera, leads to a matrix size o
6464.
b) The noise: This is caused by the statistical
fuctuations o radiation decay. The lower the
total counts, the more noise is present and, i
the matrix size is doubled (128 instead o 64),
the number o counts per pixel is reduced by
a actor o 4. 128128 matrices produce ap-
proximately three times more noise on the
image ater reconstruction than do 6 x 6
matrices (Garcia et al. 1990).
The planar images (or static projections) do
not have the reconstruction problem and can
be acquired over longer times so a 256 256
matrix is commonly used.
Zoom actor
The pixel size is dependent on the camera
eld o view (FOV). When a zoom actor o
1.0 is used, the pixel size (mm) is the useul
FOV (UFOV, mm) divided by the number o
pixels in one line. When a zoom actor is used,
the number o pixels per line should rst be
multiplied by this actor beore dividing it intothe FOV.
Example:
Acquisition with matrix 128, zoom 1.0 and
UFOV 400 mm. Pixel size: 400/128=3.125 mm.
The same acquisition with a zoom actor o 1.5.
Pixel size: 400/(1.5128)=2.08 mm.
It is important to check this parameter be-
ore the acquisition, as it is very oten used in
parathyroid imaging, especially i a subtraction
technique is used.
Preerred orbit
Either circular or elliptical orbits can be used
in SPECT imaging (Fig. 1). A circular orbit (Fig.
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Chapter 3: Imaging equipment - preparation and use
With a circular orbit, the camera is distant rom
the body at some angles, causing a reduction
in spatial resolution in these projections. This
will reduce the resolution o the reconstructed
images.
With an elliptical orbit, spatial resolution will be
improved as the camera passes closer to the
body at all angles. Nevertheless, the distance
rom the organ to the detector varies more
signicantly with an elliptical orbit than with
a circular orbit. This may generate arteacts
simulating small photopenic areas when re-
constructing using ltered back projection.
Programmes that allow the camera to learn
and closely ollow the contours o the body
are available and improve resolution, although
at the expense o computing power to modiy
the data beore reconstruction.
The loss o spatial resolution with a circular
orbit has to be oset against the potential ar-
teacts that may be generated by an elliptical
or contoured orbit.
Filtered back projection image
reconstruction: some considerations
The main goal o nuclear medicine parathy-
roid imaging procedures is to identiy the
site o parathyroid hormone production,
usually a single parathyroid adenoma. How-
ever, parathyroid adenomas can be ound in
diverse locations: alongside, beside or within
the thyroid, or in anatomical regions distantrom thyroid, such as high or low in the neck
and mediastinum. The diversity o these ana-
tomical locations makes SPECT a useul tool
in parathyroid imaging.
Furthermore, parathyroid adenomas are small
structures with increased uptake oten close
to normal thyroid activity. The choice o an
optimum lter when using ltered back pro-
jection or reconstruction is crucial (Pires Jorge
et al. 1998).
A lter in SPECT is a data processing algorithm
that enhances image inormation, without
signicantly altering the components o the
input data, creating arteacts or losing inor-
mation. It should produce results that lead to
Figure 1a circular orbit
Figure 1b elliptical orbit
Figure 1a Figure 1b
1a) is dened by a xed distance rom the axis
o rotation to the centre o the camera surace
or all angles. Elliptical orbits (Fig. 1b) ollow
the body outline more closely.
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a correct diagnosis. Incorrect or over-ltering
may produce adverse eects by reducing ei-
ther resolution or contrast, or by increasing
noise.
A lter in SPECT, being a processing algorithm,
operates in the requency-amplitude domain,
which is obtained rom the spatial domain by
the Fourier transorm. In the spatial domain,the image data obtained can be expressed by
proles o any matrix row or column show-
ing the activity distribution (counts) as a unc-
tion o distance (pixel location). The Fourier
method assumes that this prole is the sum
o several sine and cosine unctions o dier-
ent amplitudes and requencies. The Fourier
transorm o the activity distribution o a given
prole is a unction in which the amplitude othe sine or cosine unctions is plotted against
the corresponding requency o each. This rep-
resentation is also called the image requency-
amplitude domain.
In input data, the highest requency that
can be measured is named the Nyquist re-
quency, which is determined by the matrix
size as well by the scintillation detector size
and is expressed by the ormula: fn=1/(2d)
where fn is the Nyquist requency and dis the
acquisition pixel size. For example, when using
a 6464 matrix with a 41-cm gamma camera
UFOV, the pixel size (d) is 0.64 cm. Thereore
the Nyquist requency is 0.78. This means that
any input data where the requency is higher
than 0.78 cannot be measured.
The input data plotted in the image requen-
cy-amplitude domain present three com-
ponents that are partially superposed: the
low-requency background, useul or target
data and the high-requency noise. Here back-
ground does not mean surrounding natural
radiation or surrounding non-tissue activity
but rather the low-requency waves gener-
ated by the reconstruction process, such asthe well-known star arteact that appears in
an unltered back projection. The high-re-
quency noise is related to background and
scatter radiation or statistical count fuctua-
tions during SPECT acquisition, which may
induce image distortions.
Usually SPECT ltered back projection couples
a ramp lter with an additional ltering (e.g.Hann, Hamming, Parzen). The ramp lter is
so called as its shape looks like a ramp and
it will eliminate an important portion o the
unwanted low-requency background. How-
ever, the ramp lter amplies the contribution
o the high-requency noise to the image. This
is why it is recommended that an additional
lter be coupled with the ramp lter in order
to smooth an image where some details could
appear very noisy. The degree o smoothing
or each additional lter is under the control
o the user, as s/he has to decide the cut-
o requency at which the lter will be ap-
plied. The cut-o requency is the requency
value that denes the maximum requency
acceptable (which may contain useul data)
while ignoring the higher requency noise.
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Chapter 3: Imaging equipment - preparation and use
Obviously the maximum value o the cut-o
requency or a given additional lter is the
Nyquist requency.
As parathyroid adenomas appear as small hot
spots, requently within normal thyroid activ-
ity, the optimum choice o lter is a high-pass
type lter with a cut-o requency value close
to the Nyquist requency. A high-pass typelter will be applied in order to eliminate the
background image components (low requen-
cy) and conserve target data, although some
noise (high requency) will have to be toler-
ated because o the low image smoothing.
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Patient preparationAudrey Taylor and Nish Fernando
Patient identication
To minimise the risk o a misadministration:
Establish the patients ull name and other
relevant details prior to administration o
any drug or radiopharmaceutical.
Corroborate the data with inormation pro-
vided on the diagnostic test reerral.
I the inormation on the reerral orm does
not match the inormation obtained by the
identication process, then the radiopharma-
ceutical/drug should not be administered to
the patient. This should be explained to the
patient and clarication sought as soon as
possible by contacting the reerral source.
The patient/parent/guardian/escort shouldbe asked or the ollowing inormation, which
should then be checked against the request
orm and ward wristband in the case o an
in-patient:
Full name (check any spellings as appropri-
ate, e.g. Steven vs Stephen)
Date o birth
Address
I there are any known allergies or previous
reactions to any drug, radiopharmaceutical,
iodine-based contrast media or products
such as micropore or Band-Aids
A minimum o TWO corroborative details
should be requested and conrmed as cor-
rect.
The ollowing inormation should be checked
with the patient/parent/guardian/escort
where appropriate:
Reerring clinician/GP/hospital
Any relevant clinical details
Conrmation that the patient has complied
with the dietary and drug restrictions
Conrmation that the results o correlative
imaging (e.g. echocardiography, angiogra-
phy, etc.) are available prior to the study, andnoting o any recent interventions
I in doubt, do not administer the radiophar-
maceutical or drug and seek clarication.
Specic patient groups
This is a guide only. Patients who are unable to
identiy themselves or any o a variety o rea-
sons should wear a wrist identication band.
Hearing diculties: Use written questions
and ask the patient to supply the inormation
verbally or to write their responses down.
Speech diculties: Ask the patient to write
down their name, date o birth and address
and other relevant details.
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Chapter 4: Patient preparation
Language diculties: I an accompanying
person is unable to interpret the questions,
then the study should be rebooked when
a member o sta or relative with the ap-
propriate language skills or an interpreter
is available.
Unconscious patient: Check the patients
ID wristband or the correct name and dateo birth. I no wristband is attached, ask the
nurse looking ater the patient to positively
conrm the patients ID.
Conused patient: I the patient is an in-pa-
tient, check the patients ID wristband or
the correct name and date o birth. I no
wristband is attached, ask the nurse looking
ater the patient to positively conrm thepatients ID. I the patient is an out-patient,
ask the person accompanying the patient
to positively conrm the patients ID.
I a relative, riend or interpreter provides in-
ormation re the patients name, date o birth
etc., it is advisable or them to sign so as to
provide written evidence conrming the rel-
evant details.
Patients can be required to send in a list o
medications, approximate height, weight and
asthma status so that stressing drugs can be
chosen in advance. They should be advised to
contact the department i they are diabetic so
as to ensure that the appropriate guidance is
given with regard to eating, medication etc.
A ull explanation o the procedure should be
given, including, risks, contraindications and
side-eects o stress agents used, time taken
or scan, the need to remain still etc.
I the patients are phoned prior to appoint-
ment, it acts as a reminder o the test and
gives the patient an opportunity to discuss
any concerns.
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QUESTIONNAIRE FOR ALL FEMALE PATIENTS OF CHILD BEARING AGE
(12 55 YEARS)
We are legally obliged under The Ionising Radiation (Medical Exposure) Regulations 2000
to ask emales o child bearing age who are having a nuclear medicine procedure whether
there is any chance they may be pregnant or breasteeding.
Prior to your test, please answer the ollowing questions in order or us to comply with
these regulations:
PATIENT NAME ................................................................................................................................... D.O.B
1. Have you started your periods? (please tick appropriate box)
Y What is the date o your last period ...................................................................
N Please sign below and we can then proceed with your test
OR Have you nished your periods / had a hysterectomy (please tick appropriate box)
Y Please sign below and we can then proceed with your test
N What is the date o your last period
2. Is there any chance you may be pregnant (please tick appropriate box)
Y We will need to discuss your test with you beore we proceed
Not sure We will need to discuss your test with you beore we proceed
N Please sign below and we can then proceed with your test
3. Are you breasteeding? (please tick appropriate box)
Y We will need to discuss your test with you beore we proceed
N Please sign below and we can then proceed with your test
Pregnancy
Women o childbearing potential should have their pregnancy status checked using a orm
such as the example below:
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Chapter 4: Patient preparation
I have read and understood the questions above and conrm that I am not pregnant or
breasteeding and that I am aware that ionising radiation could damage a developing
baby.
Signed: ____________________________________ Date: _____________________
(Patient)
For all patients under 16 years o age
I have read and understood the question above and conrm that the patient named is not
pregnant or breasteeding
Signed: ____________________________________ Date: _____________________
Parent Guardian (please tick appropriate box)
THIS FORM WILL BE CHECKED / DISCUSSED PRIOR TO THE START OF THE TEST
The operator administering the radiopharma-
ceutical should advise the patient on minimis-
ing contact with pregnant persons and chil-
dren. In addition, the operator administering
the radiopharmaceutical should check that
any accompanying person is not pregnant
(e.g. escort nurse)
Parathyroid patient preparation
I possible, and under guidance rom the
reerring clinician, the patient should be o
any thyroid medication or 46 weeks prior
to imaging.
Establish whether the patient has had any
imaging procedure using iodine contrast
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within the last 6 weeks (CT with contrast,
IVU etc). Allow a period o 6 weeks between
these procedures and thyroid imaging.
Iodine-containing medications may have to
be withdrawn, and the reerring clinicians
advice should be sought. These medica-
tions include: propylthiouracil, mepro-
bamate, phenylbutazone, sulphonamides,corticosteroids, ACTH, perchlorate, anti-
histamines, enterovioorm, iodides, Lugols
solution, vitamin preparations, iodine oint-
ments and amiodarone.
Beore any pharmaceuticals are ordered,
check whether the patient has had a total
thyroidectomy. I this is the case, then the
subtraction technique should not be car-ried out and consideration should be given
to undertaking a dual-phase 99mTc-sestamibi
study.
Ask the patient whether he or she has any
thyroid disorders such as thyrotoxicosis,
hypothyroidism, thyroid nodules or thy-
roid goitre. These conditions can increase
instances o alse-positive 99mTc-sestamibi
uptake and also aect 123I sodium iodide
uptake. In the case o hypothyroidism, do
not carry out the subtraction technique and
consider undertaking a dual-phase 99mTc-
sestamibi study.
Ask the patient whether he or she is able to
lie supine or the duration o the study and
also whether he or she is claustrophobic.
Consider another imaging modality i the
patient cannot lie still or the duration o the
study owing to discomort or anxiety.
Although 123I sodium iodide contains little
carrier-ree iodide, it is important to ask
the patient about any adverse reactions
to iodide in the orm o contrast media ormedication. I positive, seek the advice o
the lead clinician.
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Imaging protocolsNish Fernando and Sue Huggett
There are many variations in the imaging pro-
tocols used. For dual-isotope studies where
images are acquired sequentially with the sec-
ond nuclide being injected ater the rst set o
images, consideration must be given to timing
o uptake and downscatter rom the higher
energy nuclide when considering which
nuclide to use rst. O course, simultaneous
imaging, although aected by downscatter,obviates problems o image registration.
One subtraction and one washout technique
are described, including SPECT imaging, as ex-
amples only. Explanations have been given or
the choices so that adaptations can be made
with knowledge o their eects.
SPECT/CT has been suggested as a suitabletechnique to increase the sensitivity o de-
tection (Gayed et al. 2005) but is beyond the
scope o this booklet.
123I sodium iodide/99mTc-sestamibi
subtraction
Give a ull explanation o the procedure to the
patient. In particular, stress the importance
o keeping still during the acquisition.
Ensure good venous access. A venon with
a three-way tap system into a vein in the
patients arm or the back o the hand is
more convenient than a butterfy needle
as veins more requently collapse around a
buttery needle than around the plastic o a
venon. Also, the patient has more reedom
o movement i a venfon is inserted.
Inject 123I sodium iodide ollowed by a saline
ush o 10 ml. Wrapping a bandage around
the arm or hand where the venfon is sited
will protect it during the period o delay.
At 0 min post 123I injection, ask the pa-
tient to empty the bladder. Ask the pa-tient whether he or she understands the
procedure. Again, stress the importance
o keeping still.
At 50 min post 123I injection, position the pa-
tient supine on the gamma camera couch.
Ensure the neck is extended by positioning
his/her shoulders on a pillow. Use sand-
bags and a strap to immobilise the headand neck. Ensure the patient is comortable
and understands the need to keep still. A
pillow placed underneath the knees can
reduce back discomort.
Position the patient so that an anterior image
o the thyroid and mediastinum can be ob-
tained, allowing any ectopic tissue to be in-
cluded in the image. Place the patients arm
that has the venfon and three-way system
onto an arm rest. Ensure patency o the ven-
fon by fushing through with saline. Re-site
the venfon i the vein has collapsed.
Start acquisition at 60 min post 123I sodium
iodide injection using a dual-isotope dy-
namic acquisition with non-overlapping
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windows or 99mTc (-10% to +5% about
the peak at 140 keV) and 123I (-5% to +10%
about the 159-keV peak).
Acquire 2-min rames or 20 min using a
zoom o .0 and a matrix o 128128. A
dynamic acquisition is preerable to a static
one as movement correction, provided it is
in the x- or y-direction, can be applied to theimages. The large zoom is chosen in order
to increase spatial resolution. However, this
will increase noise in the image and so the
acquisition must be o sucient duration
to compensate or this.
Pure iodide images may be acquired or 10
min. As well as being critical or processing,
these pure iodide images can be benecialin reducing alse-positive cases due to thy-
roid disease.
Without any patient movement, inject 99mTc-
sestamibi ollowed by a 10-ml saline fush,
between the 11th and 12th minute and
continue the acquisition or 30 min.
As a large zoom has been used, it is advis-
able at the end o the dynamic acquisition
to carry out an unzoomed image to include
the salivary glands and the heart. This will
ensure the detection o any ectopic para-
thyroid glands, which can occur in the re-
gion o the unzoomed image. Acquire this
image on the same dual-isotope settings or
300 s onto a matrix o 256256.
Processing
In order to detect the increased uptake o99mTc-sestamibi in the parathyroid tissue it is
necessary to subtract the 123I image rom the
99mTc-sestamibi image.
The precise computer protocol will vary rom
centre to centre and even rom camera system
to camera system. However, all protocols willollow the same basic steps.
Movement correction
As the images have been acquired simultane-
ously, there will be no need to match the posi-
tions by shiting either image, but the images
should be checked or movement and any
correction algorithms applied beore com-
mencing. This can be as simple as checkingall the rames and rejecting any with blurring
beore the rames are summed. This will not
help i the patient has moved to a dierent
position rather than having coughed or swal-
lowed deeply and returned to the original
position.
I overall movement has occurred, the situa-
tion may be rescued i the subsequent rames
can be shited by reerence to some standard
point (sometimes the hottest pixel) or even
by eye.
The subtraction
Both sets o rames (corrected i necessary)
are summed to make one 99mTc and one 123I
image.
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Chapter 5: Imaging protocols
There will be more counts in the thyroid on the123I image, so it must be matched to the 99mTc
image beore subtraction and a scaling actor is
used so that the counts in the subtraction im-
age are reduced by this actor, pixel by pixel.
The simplest technique reduces the image
to be subtracted to, or example, 30%, 0%,
50%, 60% and 70% o its original values, andthese images are subtracted in turn rom the99mTc-sestamibi image, that which gives the
best result or eliminating the thyroid tissue
being chosen by eye.
A more automated system will draw a region
o interest around the normal thyroid on the123I image by allowing the operator to choose
the count contour line which best represents itsedges. The counts in this region are then com-
pared against the counts in the same region on
the 99mTc image. The scaling actor is calculated
rom the ratio o these two values. This adjusted
image is then subtracted rom the 99mTc image
and the results displayed as a new image. Again,
there are usually two or three options oered or
the operator to choose the best result.
SPECT imaging
Additional SPECT imaging gives increased
sensitivity and more precise anatomical lo-
calisation. Acquiring both early and delayed
SPECT can be a useul addition to either the
dual-phase 99mTc-sestamibi method or the
dual-isotope 123I/99mTc-sestamibi subtraction
method.
Early SPECT should be acquired 1030 min
ater the 99mTc-sestamibi injection and de-
layed SPECT at around 3 h post injection.
The camera is peaked or both 99mTc and123I as beore.
An 180o acquisition optimises the time close
to the area o interest and attenuation isnot a problem with structures so close to
the body surace.
Acquisition should start with the camera
head at 270o; proceed in a clockwise rota-
tion and stop at 90o.
I the acquisition is carried out on a double-
headed camera, a 90o L-Mode SPECT will beuseul and more counts will be collected as
both heads are used or the acquisition.
Contouring can be used i available, al-
though the patient should be warned i
the camera will move closer during the
acquisition.
It should be ensured that the zoom chosen
allows adequate coverage o the mediasti-
num to locate any ectopic glands there.
Using a zoom o 2 will ensure better spatial
resolution than no zoom, and there should
be enough coverage o the mediastinum.
A 6464 matrix is sucient or the expected
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resolution and will optimise counts per pixel
and hence reduce noise.
30 60-s rames is manageable or the patient
and will maximise counts in the image.
For delayed SPECT, increasing the time
per projection to 90 s will restore the total
counts.
Processing
The data may be reconstructed using the
methods o ltered back projection or itera-
tive reconstruction. Streak arteacts may be
seen in data reconstructed by ltered back
projection and these will not occur or the
iterative method.
The raw data can be viewed as a rotating
image and the limits or the region to be
reconstructed chosen.
The region should extend rom the parotid
glands to the mediastinum to locate any
ectopic tissue.
The reconstruction programme with cho-
sen lters is initiated.
Once the reconstruction is completed, the
images are viewed in the transverse, coronal
and sagittal planes.
Datasets can be viewed as volumetric dis-
plays as well as tomographic slices.
99mTc-sestamibi washout technique
I 99mTc-sestamibi is used alone, the two sets
o images (early and delayed) are inspected
visually.
740 MBq 99mTc-sestamibi is injected using the
same protocols or patient preparation, i.e.
ID and LMP checks/explanation to patient as
beore and imaging typically at 10 min and23 h
The camera is peaked or technetium and
a low-energy high-resolution collimator
can be used as images can be taken or
a sucient time to avoid statistical noise
problems and pinhole collimators are used
in some centres. Zoom can be used but
remember the possibility o ectopic tissue.
Neck and mediastinum views are taken with
patient positioning as beore. Again, a single
view o 600 s counts can be taken or a series
o 1060-s rames acquired so that move-
ment arteacts can be corrected.
The same parameters and positioning must
be used or the 10-min and late views
Right and let anterior oblique views can be
obtained i required.
SPECT can be used in this case also.
All lms should be correctly annotated with L,
R and anatomical markers and labelled.
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Technical aspects o probe-guided surgery orparathyroid adenomasDomenico Rubello
Bilateral neck exploration (BNE) still represents
the gold standard approach in patients with
primary hyperparathyroidism (pHPT). Howev-
er, surgical approaches to pHPT patients have
altered signicantly in many surgical centres
during the past decade, with the development
o minimally invasive parathyroidectomy using
endoscopic surgery or radio-guided surgery
(MIRS). This development can be attributed totwo main reasons: (a) the consciousness that
pHPT is due to a single parathyroid adenoma
in the majority o patients (at least 85%), and
(b) the technical improvements introduced
into surgical practice with the availability o
microsurgery instruments, endoscopes, intra-
operative measurements o quick parathyroid
hormone (QPTH) and gamma probes.
New approaches to minimally invasive para-
thyroidectomy consisting in the removal o a
solitary parathyroid adenoma via a small 12
cm skin incision have been widely adopted. O
course, in contrast to BNE, minimally invasive
parathyroidectomy always requires accurate
preoperative imaging in order (a) to establish
whether the parathyroid adenoma is eec-
tively solitary and (b) to locate precisely the
enlarged gland. The present chapter ocusses
mainly on technical aspects o the MIRS tech-
nique. Moreover, the MIRS technique devel-
oped in our centre is based on the injection
o a very low 99mTc-sestamibi dose 37 MBq
compared with the traditional MIRS tech-
nique, which uses a high 99mTc-sestamibi
dose 740925 MBq.
Selection criteria or ofering MIRS
When planning MIRS (unlike when perorm-
ing BNE), strict inclusion criteria need to be
ollowed: (a) evidence at 99mTc-sestamibi scin-
tigraphy o a solitary parathyroid adenoma;
(b) intense 99mTc-sestamibi uptake in the para-
thyroid adenoma; (c) absence o concomitant
thyroid nodules at 99mTc-sestamibi scintigraphy
and high-resolution (10 MHz) neck ultrasound;(d) no history o amilial HPT or multiple endo-
crine neoplasia; and (e) no history o irradia-
tion to the neck. O note, previous thyroid or
parathyroid surgery is not a contraindication
to MIRS. When these inclusion criteria are
adopted, approximately 6070% o pHPT pa-
tients can be oered MIRS. The main reason or
exclusion is the presence o 99mTc-sestamibi-
avid thyroid nodules, which, by mimicking aparathyroid adenoma, can cause alse posi-
tive results during surgery. Figure 1 shows a
patient scheduled or MIRS while Fig. 2 shows
a patient excluded rom MIRS.
Preoperative imaging protocol
In our protocol, preoperative imaging proce-
dures include single-session 99mTc-sestamibi
scintigraphy and neck ultrasound (Norman
and Chheda 1997; Costello and Norman
1999; Mariani et al. 2003; Rubello et al. 2000).
In patients with concordant 99mTc-sestamibi
and ultrasound results (both positive or nega-
tive), no urther imaging is perormed, while
in cases with discrepant ndings (99mTc-sesta-
mibi positive and US negative) a tomographic
(SPECT) examination is obtained to investi-
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gate a possible ectopic or deep position o the
parathyroid adenoma. SPECT is obtained just
ater the completion o planar 99mTc-sestamibi
scintigraphy, thus using the same radiotracer
dose; in this way, 99mTc-sestamibi re-injection is
not necessary, thus avoiding additional radia-
tion exposure to the patient and personnel.
In other centres, preoperative 99mTc-sestamibi
scintigraphy alone is considered a sucienttool or the planning o MIRS.
Intra-operative MIRS protocol
Table 1 shows the steps in the MIRS protocol
used in our centre.
A collimated gamma probe is recommended
with an external diameter o 111 mm. A
non-collimated probe, which can be used orsentinel lymph node biopsy, is not ideal or
parathyroid surgery owing to the relative com-
ponent o diuse and scatter radioactivity de-
riving rom the anatomical structures located
near to the parathyroid glands, mainly related
to the thyroid gland. Probes utilising either a
NaI scintillation detector or a semiconductor
detector have proved adequate or MIRS.
A learning curve o at least 2030 MIRS op-
erations is recommended or an endocrine
surgeon. During these, the presence in the
operating theatre o a nuclear medicine phy-
sician is usually considered mandatory. In
the opinion o the writer, the presence o a
nuclear medicine technician, with expertise
in probe utilisation, is very useul in helping
the surgeon to become more skilled in the
use o the probe.
The probe is usually handled by the surgeon,
who should measure radioactivity in dier-
ent regions o the thyroid bed and neck in an
attempt to localise the site with the highest
count rate beore commencing the operation.
This site is likely to correspond to the parathy-roid adenoma. Then, during the operation, the
surgeon should measure the relative activity
levels in the parathyroid adenoma, thyroid
bed and background. Moreover, a check o
the empty parathyroid bed ater removal
o the parathyroid adenoma is a very useul
parameter to veriy the completeness o re-
moval o hyperunctioning parathyroid tissue.
Ex vivo measurement o any removed surgicalspecimen should be done to veriy the total
clearance o the parathyroid adenoma. The
calculation o tissue ratios parathyroid to
background (P/B) ratio, thyroid to background
(T/B) ratio, parathyroid to thyroid (P/T) ratio
and the empty parathyroid bed to background
(empty-P/B) ratio can be useul in evaluating
the ecacy o MIRS. The tissue ratios obtained
in a large series o 355 pHPT patients operated
on in our centre are reported in Table 2.
Attention has to be given to avoidance o
intra-operative alse negative results due to99mTc-sestamibi-avid thyroid nodules and to
stagnation o the radiotracer within vascular
structures o the neck and thoracic inlet: in this
regard, the careul acquisition and evaluation
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Table 1. Steps in minimally invasive radioguided surgery (MIRS) o parathyroid adenomas using
the low 99mTc-sestamibi dose protocol developed in our centre
Blood samples are drawn rom a peripheral vein both beore commencing surgery and 10 min
ollowing the removal o the parathyroid adenoma to measure intra-operative QPTH levels
37 MBq o99mTc-sestamibi is injected in the operating theatre 10 min beore the start o
surgery
Prior to surgical incision, the patients neck is scanned with an 11-mm collimated probe to
localise the site with the highest count rate, corresponding to the cutaneous projection o
the parathyroid adenoma
A transverse midline neck access (approximately 1 cm above the sternal notch) is preerred
because conversion to BNE is easily obtained i necessary
An 11-mm collimated probe is repeatedly inserted through a 2-cm skin incision, guiding the
surgeon to the maximum count rate area corresponding to the parathyroid adenoma
In some patients with a parathyroid adenoma located deep in the neck, ligature o the middle
thyroid vein and o the inerior thyroid artery is required
Radioactivity o the parathyroid adenoma, thyroid gland and background is measured with
the probe
Radioactivity is measured ex vivo to conrm successul removal o parathyroid tissue
Radioactivity o the empty operation site is checked to evaluate the completeness o para-
thyroid tissue removalTissue ratios are calculated (P/B, P/T etc.)
QPTH, quick parathyroid hormone; BNE, bilateral neck exploration; P/B, parathyroid to back-
ground ratio; P/T, parathyroid to thyroid ratio
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Chapter 6: Technical aspects of probe-guided surgery for parathyroid adenomas
tamibi dose protocol, with a success rate in
the intra-operative detection o parathyroid
adenoma o approximately 9698%, without
major intra-operative surgical complications. It
is likely that Normans single-day protocol will
be preerable in patients with a low likelihood
o nodular goitre whilst our dierent-day pro-
tocol appears preerable in areas with a higher
prevalence o nodular goitre.
Irrespective o the type o MIRS protocol used,
the principal advantages o MIRS over tradi-
tional BNE can be summarised as: (a) a small
skin incision with avourable cosmetic results,
(b) a shorter operating time, (c) the possibility
o perorming MIRS under local anaesthesia,
(d) a shorter hospital recovery time, (e) the
possibility o same-day hospital discharge, ()
lower post-surgical time and (g) lower costs.
Table 2. Probe tissue ratios calculated during MIRS or parathyroid adenoma removal (n=355
pHPT patients)
P/B ratio = 1.64.8 (mean 2.60.5)
P/T ratio = 1.12.8 (mean 1.50.4)
T/B ratio = 1.51.8 (mean 1.60.1)
Empty-P bed/B ratio = 0.91.1 (mean 1.00.03)
TN/P ratio = 0.51.5 (mean 1.00.4)
P=parathyroid
T=thyroid
B=background
TN=thyroid nodule
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Table 3. Radiation dose to operating theatre personnel during MIRS with the low (37 MBq)99mTc-sestamibi dose protocol used in our centre
Gy/hour Gy/year*
Surgeons body 1.2 120
Surgeons hands 5.0 500
Anaesthesiologist 0.7 70
Instrument nurse 1.1 110
Other nurses 0.1 10
*Estimated or 100 interventions, each lasting 60 min
Figure 1. Preoperative dual-tracer parathyroid subtraction scintigraphy. Left image: 99mTc-pertech-
netate scan showing a normal thyroid gland. Middle image: 99mTc-sestamibi scan showing an
area o radiotracer uptake juxtaposed to the lower pole o the let thyroid lobe. Right image:
Subtraction (99mTc-sestamibi-99mTc-pertechnetate) image, clearly showing a let inerior para-
thyroid adenoma. This patient was oered MIRS.
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Chapter 6: Technical aspects of probe-guided surgery for parathyroid adenomas
Figure 2. Preoperative dual-tracer parathyroid subtraction scintigraphy. Left image: 99mTc-pertech-
netate scan showing a multinodular goitre with some hyperunctioning nodules (three in the
right thyroid lobe, one in the let thyroid lobe). Middle image: 99mTc-sestamibi scan showing
a picture similar to the 99mTc-pertechnetate image plus a let superior area o exclusive 99mTc-
sestamibi uptake. Right image: subtraction (99mTc-sestamibi-99mTc-pertechnetate) image clearly
showing a let superior parathyroid adenoma. This patient was excluded rom MIRS due to the
coexistence o a solitary parathyroid adenoma and multinodular goitre with multiple99m
Tc-sestamibi-avid thyroid nodules in both thyroid lobes
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