2. „In vivo” · 2 ⋅ 511 keV Varga J, 2011 Introduction to Nuclear Medicine. 9 Producing artificial radioactive material Stanley Livingstone and Ernest Lawrence with their 8

Introduction to

NUCLEAR MEDICINE

Introduction to

NUCLEAR MEDICINE

Department of Nuclear Medicine

University of Debrecen

József Varga

2011.2

Nuclear Medicine: ManualsNuclear Medicine: Manuals

• Link to English reference manual:

http://www.auntminnie.com/index.asp?sec=ref&sub=ncm

• Lectures in English:http://www.nmc.dote.hu/nmt_eng/oktatas_e.htm

• In Hungarian:

http://www.nmc.dote.hu/nmtk/index.html

• Book: A Nukleáris Medicina Tankönyve(Szerk. Szilvási I.; B+V Kiadó, 2002, 2010)

• Required reading:Taylor A., Alazraki N., and Schuster D.M.:A Clinician's Guide to Nuclear Medicine (2nd Edition)

The Society of Nuclear Medicine, Reston, 2006

ISBN: 0972647872

Varga J, 2011 Introduction to Nuclear Medicine

3

1924: Principle of radiotracer

applications:

Changing an atom in a molecule for its radioisotope will not change its

chemical and biological behaviour

significantly.

Consequence: the movement, distribution,

concentration of the molecule can be

measured with radiation detectors.

György HEVESY (1885-1966)

1943 Nobel Laureate in

Chemistry

„for his work on the use of

isotopes as tracers in the study of

chemical processes”

NUCLEAR MEDICINENUCLEAR MEDICINE

Varga J, 2011 Introduction to Nuclear Medicine 4

Medical & biological applications of radionuclidesMedical & biological applications of radionuclides

Medical applications

(nuclear medicine)

Research applications

(nuclear medicine)

Diagnostics

Therapy

„In vivo”

imaging

„In vitro”

Application of diagnostic

methods for research

„Molecular imaging”

Combination of analitical

laboratory methods with

radiotracer technique

„In vivo”

non-imaging


5

ROSALYN YALOW

(1921-)

1977 Nobel Laureate in Medicine

„for the development of

radioimmunoassays of peptide

hormones”

1960: Yalow and Berson developed a radioassay for measuring

Insulin concentration from plasma samples

(saturation analysis)

RIA: radioimmunoassay(competitive protein binding;

the ligand is labeled)IRMA: immunoradiometric assay

(„sandwich” assay)

Fields of Nuclear Medicine:

1. „In vitro” concentration measurements


1. „In vitro” concentration measurements


Hal Anger (Berkeley)with his positron camera

Developer of the scintillation camera

1957: Anger camera

Principle: many photomultiplier tubes „see” the

same large scintillation crystal; an electronic circuit decodes the coordinates of each event


2. „In vivo” imaging

A. With gamma emitters („single photon”)



A. With gamma emitters („single photon”)


7


B. With positron emitters („kétfotonos”)


B. With positron emitters („kétfotonos”)

Early ‘70-s: PET

Principle: Two 511 keV photons resulting from annihilation fly in opposite directions.Their coincident detection determines the line of annihilation.

• Michel M. Ter-Pogossian, Mallinckrodt Institute

• Michael E. Phelps, UCLA


Selecting the radionuclide for imagingSelecting the radionuclide for imaging

C-11

N-13

O-15

F-18

e-

γγγγX-ray

Characteristic X-ray(following K-capture)

For external detection: electromagnetic radiation can be used!

Gamma emittersgamma energy: 80-400 keV(if lower: attenuated inside the patientif higher: low detection sensitivity)

Positron emittersannihilation radiation:

2 ⋅ 511 keV


9

Producing artificial radioactive materialProducing artificial radioactive material

Stanley Livingstone and Ernest Lawrence with their 8 MeV cyclotron

(1935)

• In nuclear reactors(high neutron flux)

• Using accelerators(circular: cyclotron)

expensive!

Ernest Lawrence(Berkeley)

inventor of the cyclotron


Radionuclides in Nuclear Medicine,

UK 2003/04

Tc-99m; 79.5%

Kr-81m; 6.1%

Cr-51; 3.8%

Tl-201; 2.4%

I-131; 2.3%

F-18; 1.5%

C-14; 1.2%

Xe-133; 0.8%

I-123; 0.7%

In-111; 0.4%

Egyéb; 1.3%

Gamma imaging

RN therapy

PET imaging


11

99Mo-99mTc generator99Mo-99mTc generator

Evacuated vial

Eluent

Filter

Air filter

Alumina column

Lead shielding


Anger (gamma) camera

1. Collimator

2. Crystal: NaI (Tl)

3. Photomultipliertubes

4. Impulses

5. Anger circuit

6. X, Y coordinates

7. „Good” events

8. Memory scope

9. Analog-digitalconverters

10. Computer

Matrix

circuitDifferential

discriminator


13

• To form an image from the detected photons, the direction of movements

should be known

• The collimator lets through only the photons that move perpendicularly to its

plane

Detector

IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ⇐⇐⇐⇐ Lead

collimator

Photomultipliers

+ preamplifiers

Source: Freek Beekman et al., Utrecht

The role of a

collimator

The role of a

collimator

Crystal


PET: ConceptPET: Concept

Varga J, 2011 14Introduction to Nuclear Medicine

15

Principle:

Beta-emitting radiopharmaceuticals go directly to the cells or tissue to be destroyed or deactivated

Very specific radiopharmaceuticals are needed

Unsealed preparation: One that mixes in the patients’ body on a molecular level(e.g. after intravenous injection)


3. Therapy with unsealed radiactive preparations


3. Therapy with unsealed radiactive preparations


Source: „What is Nuclear Medicine?” (SNM)

Medical imagingMedical imaging


17

Targets and tools of medical imagingTargets and tools of medical imaging


Average of health-care level I , 1991-96 (UNSCEAR)

1 10 100 1 000 10 000 100 000 1 000 000

X-ray, dental

X-ray, medical

CT

Angiography

Interventional

Nuclear imaging

Radionuclide therapy

Teletherapy

Brachytherapy

Number of procedures / million population

Therapy

Diagnosis

United Nations Scientific Committee on the Effects of Atomic Radiations


19

Functional vs. structural imaging:Low-grade recidive glioma (FDG)

PET Center,

Debrecen

Varga J, 2011 Introduction to Nuclear Medicine 20Varga J, 2011 Introduction to Nuclear Medicine

21

Detection sensitivity of imaging techniquesDetection sensitivity of imaging techniques

Imaging Concentration of tracer / „contrast”

technique material (mol/kg body mass)

UH 10-3

CT 10-3

Gamma camera 10-9- 10-12

PET 10-9- 10-12

MRI 10-5

MRS 10-5

Source: G. von Schulthess, University Hospital, Zürich


Static:Imaging an equilibrium distribution

Dynamic:Series of images following the accumulation /metabolic pathways / secretion of a radiopharmaceutical

Whole body:Static images connected

Tomographic:Single Photon Emission Computed Tomography (SPECT)Positron Emission Tomography (PET)

Emission imaging: Study typesEmission imaging: Study types


23

Whole body

bone scintigram

Spot images


RAW image Metz-filtered

Example: Static imageThyroid scintigram without and with filtering

Example: Static imageThyroid scintigram without and with filtering


25

higher uptake is

abnormal here

„Positive” scintigram: Toxic nodular goiter„Positive” scintigram: Toxic nodular goiter

Varga J, 2011 Introduction to Nuclear Medicine Varga J, 2011 Introduction to Nuclear Medicine 26

Different molecules have different distribution Malignant thyroid tumor

Different molecules have different distribution Malignant thyroid tumor

99mTc-Pertechnetate

Decreased activity with pertechnetate

Increased MIBI accumulation

99mTc-MIBI

27

Examples: Dynamic studiesExamples: Dynamic studies

Kidney Esophagus Gated blood pool


Time-activity curves from regions Parametric images

Image series

Calculate a parameter of the time-activity curve for

each pixel

Display with pseudo-colors

Outline Regions of Interest

Create time-

activity curves from the ROIs

Information from dynamic studiesInformation from dynamic studies


29

SPECT: „Single Photon Emission Computed

Tomography”

SPECT: „Single Photon Emission Computed

Tomography”

• Generally 360° arc

• For the heart: 180°

• Images at 3-6°

(30-120 projections)

• Calculation of distributionsin transaxial slices

• Reslicing along the organ(transversal, coronal, sagittal)


Gamma camerasGamma cameras


31

BackprojectionBackprojection

Projections utilized: 1 3 4

16 32 64


3 dimensional

cine display

3 dimensional

cine displayBrowser viewBrowser view

33

PET - advantagesPET - advantages

• Coincidence detection at 180°:- higher sensitivity- better signal/noise ratio

• Easier attenuation correction(sum of the two paths inside =body thickness)

• More physiologic radiopharmaceuticals(C-11, N-13, O-15, F-18)

• Dynamic tomography is possible(simultaneous acquisition from all projections)

*


Brain receptor imagingPET ligands for imaging various receptor systems

Brain receptor imagingPET ligands for imaging various receptor systems

[F-18]-memantin

(NMDA-receptor)

[F-18] fluoro-2-

deoxy-glucose

O

OH

F

HO

OH

HO

N

SCH3NH2

FH2C

CH3

Cl

OH

Cl

OCH3

NHN

O CH2CH3

N

N

N

F

O

OCH2CH

3

O

CH3

NH3C

H

H Cl

NO

Ph

[C-11]-raclopride

(dopamine D2

receptor)

[C-11]-McN 5652

(serotonin

transporter)

[C-11]-b-CPPIT

(dopamine

transporter)

[C-11]-flumazenil

(benzodiazepine-

receptor)

Source: G. von Schulthess, University Hospital, Zürich

35

Our PET is

growing up

From P. Vernon, GE


„Structure without function is a corpse;function without structure is a ghost”

37

Functional and morphological imaging:

Complementary rolesFunctional and morphological imaging:

Complementary roles

PET & SPECT CT, MR

functional information structural / morphological

information

significant partial volume effect better resolution

higher noise CT: high patient dose

attenuation and scatter degrades

images

MR: inhomogeneous image,

geometric distortion (due to

magnetic field inhomogeneity)


Hybrid devicesHybrid devices

• PET & CT or SPECT &CT on the same gantry

• Subsequent imaging,

while the patient lies in the same position


• SPECT/CT

39

Hybrid imaging, step 1: CTHybrid imaging, step 1: CT


Hybrid imaging, step 2: EmissionHybrid imaging, step 2: Emission



History: tomographyHistory: tomography

1895: X-ray (Röntgen)

1958: Gamma camera (Hal Anger)

1962: Emission reconstruction tomography (David Kuhl)

1971: CT (Godfrey Hounsfield)

CT image reconstruction (Allan M. Cormack)

197~: PET (Michel Ter-Pogossian)

1976: SPECT camera (John Keyes)Brain SPECT camera (Ronald Jaszczak)

1992: SPECT/CT, attenuation correction with CT(T. F. Lang, Bruce H. Hasegawa)

2000: PET-CT (Ron Nutt, David Townsend)

2008: Human PET/MRI

Why to use hybrid devices?Why to use hybrid devices?

1. To integrate anatomical with functional information:

• Localization

• Correction for partial volume effect

2. Attenuation correction

• Faster(shorter imaging time)

• More acurate (less noisy)


CT !!!

43

Attenuation correction of SPECTAttenuation correction of SPECT

Uncorrected(filtered backprojection)

Attenuation map Corrected(OS-EM)

Source: M. King et al.Varga J, 2011 Introduction to Nuclear Medicine 44

Tumor localization for radiation therapyTumor localization for radiation therapy


45

Effective doses (mSv)Effective doses (mSv)

0

5

10

15

20

25

Th

yro

id

Sta

t. k

idn

ey

Dy

n.

kid

ne

y (

DT

PA

)

Dy

n.

kid

ney

(M

AG

3)

Myo

card

.pe

rf.

(str

es

s+

res

t)

Bra

in p

erf

usio

n

Bo

ne

Lun

g p

erf

.

He

pa

tob

ilia

ry

Infl

am

ma

tion

(G

a)

My

oc

ard

. S

PE

CT

/CT

(s

tre

ss

+re

st)

FD

G+

LR

-CT

FD

G+

HR

CT

Intr

av

en

ous

Pye

log

ram

Bari

um

sw

allo

w

Bari

um

me

al

CT

he

ad

CT

che

st

CT

abd

om

en

CT

pelv

is

CT

(h

ea

d o

r c

he

st)

PT

CA

(h

eart

stu

dy)

Coro

na

ry a

ngio

gra

m

Ma

mm

ogra

m

Lum

bar

spin

e s

eri

es

Tho

rac

ic s

pin

e s

eri

es

Cerv

ica

l s

pin

e s

erie

s

Sk

ull (

PA

or

AP

)

Ch

es

t (P

A a

nd l

ate

ral)

Th

ora

cic

sp

ine

(A

P)

Lu

mb

ar

spin

e (

AP

)

Abd

om

en

Pe

lvis

or

hip

s

(mS

v) Scintigraphy Hybrid Complicated radiological Simple X-ray


NM, UK 2003/04

Myocardial perfusion ; 15.0%

Brain perfusion HMPAO; 0.7%

Bone Phosphates; 29.0%

Lung perfusion MAA; 14.0%

Lung ventillation ; 11.3%

Kidney, dynamic ; 5.3%

Kidney, static DMSA; 4.3%

Inflammation HMPAO; 1.2%

Thyroid Pertechnetate; 1.6%

Cardiac wall motion Tc-rbc;

1.5%

Thyroid therapy I-131; 1.5%

Tumor metabolism FDG; 1.3%

Other PET ; 0.4%

GFR Cr-51 EDTA; 3.4%

Helicobacter Pylori C-14 urea; 1.0%

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0%

SPECT

Planar

gamma

camera

Therapy

PET

Non-

imaging


Documents

2. „In vivo” · 2 ⋅ 511 keV Varga J, 2011 Introduction to Nuclear Medicine. 9 Producing artificial radioactive material Stanley Livingstone and Ernest Lawrence with their 8