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8/8/2019 Nuclear Medicine2
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Dalam Bidang Kedokteran
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Pemanfaatan Radioisotop / Senyawa
Bertanda
Sejarah dan Perkembangan Kedokteran
Nuklir
Prospek Perkembangan dalam KedokteranNuklir
Manajemen Pengobatan Kanker
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y Kedokteran Nuklir merupakan cabang ilmu kedokteranyangmenggunakan sumber radiasi terbuka berasal dari disintegrasi intiradionuklida buatan, untuk mempelajari perubahan fisiologi, anatomidan biokimia, sehingga dapat digunakan untuk tujuan diagnostik, terapidan penelitian kedokteran.
y Pembangunan Reaktordi Oak Ridge, Tenesse, USA memicu carapembuatan radioisotop yang lebih murah
y 1 Agustus 1945 : The Atomic Energy Act, US Congress memunculkan Atomic Energy Commission.
y Undang-undang ini menandai dimulainya produksi radioisotop untuk keperluan kedokteran pada reaktor di Oak Ridge
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Emilio Segre (1905-1989) Italian physicist who was co-winner of the 1959 Nobel Prize in
physics for his discovery of the antiproton. Working with Seaborg, they discovered
technetium-99m in 1938.
Hal Anger . American inventor of the scintillation scanning camera in 1958.
Gopal Subramanian (1937-2000) . Father of Tc-99m Radiopharmaceuticals.
He was an inventor and co-inventor of 11 US patents. Most of the Tc-99m RPS which
are being used today were developed by him. Perhaps the most long lasting impact of
Mani¶s work in nuclear medicine is the development of Tc-99m bone seeking agents,
which have remained in use now for more than a quarter of 35 years.
Mathew L. Thakur. Cell labeling with radioactive substances, Tc-99m and In-111
Dr. Michael E. Phelps. Original inventor of Positron Emission Tomography
(PET) in 1973.
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PERKEMBANGAN PENGGUNAAN RADIOISOTOPDi BIDANG KEDOKTERAN/KESEHATAN
Peningkatan penggunaan dalam diagnosis& terapi
Peningkatan di bidang brachytherapy Penurunan pada penggunaan cobalt therapy Penggunaan kembali beberapa radioisotop
tradisional
Pengembangan PET Litbang farmakologi (farmakokinetika & farmakodinamika)
Kompetitor teknologi lain
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Evolving Paradigm in Medicine
Imaging
Anatomy Biochemical
Therapy
Systemic Targeted
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New radiocompounds
New instruments and procedures
New approaches for old procedures
Kecenderungan Pengembangan Saat Ini
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Manajemen Pengobatan Kanker
1. Diagnosis
2. Penentuan Keparahan dan Stadium Kanker3. Memonitor Terapi
4. Prognosis
5. R
adioterapi
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1. Diagnosis
y Radiofarmaka untuk diagnosis
y Peralatan imagingy Modalitas non nuklir sebagai komplemen
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RadiofarmakaRadiofarmaka idealideal untukuntuk pencitraanpencitraan
infection/inflammationinfection/inflammation
[1] efficient accumulation and good retention
in inflammatory foci[2] rapid clearance from background[3] no accumulation in non-inflamed tissues[4] no side-effects[5] low cost (99mTc) and easy preparation
(kit formulation)[6] discrimination between infection and
non-microbial inflammation
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99mTc-HMPAO99mTc-ECD
99mTc-MIBI99mTc-Tetrofosmin
99mTc-MAG3
99mTc-EC99mTc-DTPA
99mTc-HEDSPHA
Diagnostic 99mTc-Radiopharmaceuticals
99mTc-MAA
99mTcTc--antianti CEACEA´́Carcino EmbryonicCarcino Embryonic
AntigenµAntigenµ
99mTc-SC99mTc- HIDA
Thyroid Imaging99mNaTcO4
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There are many radiopharmaceutical have beenused for diagnosing and localizing of infectionand inflammation, but to differentiate bacterialinfection from sterile inflammation is still aproblem until 1995 when Infecton wasdiscovered.
Infecton, basically is cyprofloxacine, a broadspectrum antibiotic
Invitro studies showed, that infecton can be
trapped by living pathogen bacteria and destroyDNA gyrase, but not non-pathogen bacteria
Infecton still can be trapped in bacteriasresistant to cyprofloxacine
TcTc--99m ciprofloxacin99m ciprofloxacin
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Osteomyelitis and peritoneal tb
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Tl-201/MIBI
Scintimammografi:y Pada wanita berumur 50 tahun ke bawah, glandular breasts
umumya ditemukan pada radiografi, menyebabkan kesalahan ukur 25--45% pada x-ray mammografi
y Tc-99m Sestamibi lebih sensitif dan spesifik
y Malignant lesions in patients with palpable breast abnormalitysuspected of breast cancer
y Suspected recurrent cancer following breast surgery
Kanker Lain:y Brain, bone, thyroid, lungs, soft tissue sarcomas and in low grade
lymphomas
y Of special note is the ability of Tl-201 or Sestamibi to helpdifferentiate post therapy changes from tumor recurrence.
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Scintimammography
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BONE SCANNING
Abnormal Abnormal
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Normal bone
scintigraphy
AP PA
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Ga-67 citrate
Initially it is used as a tumor imaging agent
It is used as infection agent, since its ability to localize at the site of infection (1969)
Cyclotron produced
Energy level of 91-394 keV
It binds to transferrin in the blood, which transports it to the site of infection and inflammation as a results of the increased vascular permeability of the capillaries
Adequate blood supply to the site of infection and inflammation isvery important
Accuracy of about 70-80%, but not accurate enough for distinguishing an aseptically loosened prosthesis from an infectedone (Palestro & Torres 1997)
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527079 9/23/99
Taken up by cells like glucose but not
metabolized
Correctly diagnosed the presence or absence
of active infection.
Superior to In-111 WBC in the diagnosis
chronic osteomyelitis
False positive were obtained for knee prosthesis
FF--18 FDG18 FDG
(deoxyglucose labelled with F(deoxyglucose labelled with F--18)18)
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NEW ER A OF DI AGNOSIS :
POSITRON EMISSION TOMOGR APHY
´ Ditemukan pada tahun 1973 oleh Michael E Phelps
´ Merupakan metode visualisasi metabolisme tubuh
menggunakan radioisotop pemancar positron
´ Pencitraan yang dihasilkan merupakan gambaran fungsiorgan tubuh
´ Metode pencitraan tubuh yang lain (MRI atau CT) hanya
menggambarkan kelainan bentuk organ tubuh
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POSITRON EMISSION TOMOGR APHY
Siklotron
Synthesizer Module
Camera/Scanner
Komponen-komponen PET
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PET/CT
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PET-CT SCANNER
F-18 FDG PETCT
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KELEBIH AN PET/CT
´ Data anatomi dan fungsional yang akurat dari
gabungan kamera PET dan CT mampu menyediakan
informasi diagnostik yang saling melengkapi´ Sensitifitas (lokalisasi penyakit) dan spesifisitas
(pengecualian dari pencitraan positif yang salah
akibat uptake PET-radiofarmaka secara fisiologis)
meningkat
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NEW ERA F DI AGNOSIS : SPECT-
CT
´ SPECT-CT is an emerging dual-modality imaging
technique with many established and potential clinical
applications in the field of oncology´ To date, there has been a considerable emphasis on
the benefits of integrated positron emission
tomography ² computed tomography (PET-CT) in
oncology
´ But relatively little focus on the clinical utility of SPECT-
CT
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SPECT
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CLINICAL APPLICATIONS OF
SPECT/CT´ There are some instances where sing le photon-emitting
radiopharmaceuticals are predictably more sensitive and specific:
« Endocrine-related tumors that express somatostatin receptors
« The octreotide series of sing le photon-emitting peptide tracers is far more specific for identifying the
tumor phenotype than FDG-PET.
« If we were looking for a neuroendocrine tumor based on a patient's biochemistry and symptomatology,
we would do an octreotide SPECT scan
´ Oncology applications include:
« Iodine-131 for thyroid tumors
« Tc-99m MIBI for parathyroid imaging
« Indium-111 octreotide and iodine-131 MIBG for neuroendocrine tumors
« In-131 ProstaScint for prostate cancer
« I-123 MIBG for neuroblastoma
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Penentuan Keparahan dan Stadium Kanker
Diagnosis
Terlokalisasi Metastatis
Operasi atau Terapi
Radioterapi Sistemik
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Staging Cancer
Specific OrganImaging
Whole body
Conventional PET
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Diagnosa Kedokteran Nuklir: Mendefinisikan tumor and menentukan ke
Memonitor respon terapi dengan penentuan
perubahan ukuran tumor, termasuk marker-markertumor lainnya, selama dan sesudah terapi
Memprediksi Prognosis
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Most often the tumors:
Spread in the form of two dimensional sheets, ratherthan three dimensional structures
Besides, using the structure based diagnosticprocedures: It is almost impossible to correctly distinguish viable tumor
from scar tissues, necrotic materials and granulation tissueswhich are present in variable amount in and around a tumor
following its treatment with radiation or chemotherapeuticagents.
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Functional imaging using radionuclidesprovides an excellent opportunity: to determine the response and identify presence of
viable tumor tissue during or following chemo orradiotherapy
thereby aiding the treating physician to takedecisions with respect to: continuation, modification or abandoning a particular
form of treatment.
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PrognosisPrognosis
Differential uptake of radiolabeled compounds
may permit characterization of lesions which maynot be distinguishable at the histopathologylevel.
Uptake changes may provide the earliest
evidence of therapeutic response. Tc-99m lipophillic cations may allow to identify
patients with multi-drug resistant phenotypes.
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Before treatment
Lymphoma staging
After the 2nd cycle
& effect of therapy
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TERAPI RADIONUKLID A
´ Non-invasive
´ Invasive
´ Exploit the physiology unique to an organ ora neoplasm
´ Mechanical delivery
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01 Thyroid I-131 Iodine is actively accumulated
metabolized in the thyroid
gland
02 Metastatic Bone Pain Sr-89, P-32,
Sm-153 EDTMP,
Re-188 HEDP
These are bone seeking radio-
pharmaceuticals, actively taken
up by the sites of bone
metastases
03 Malignant
phoeochromo-
cytoma and neuro-endocrine tumours
I-131 MIBG These tumours preserve the
unique ability to concentrate
metaiodo-benzyleguanidine(MIBG)
04 Liver cancer
(Hepatocellular
carcinoma)
I-131 Lipiodol,
Re-188 Lipiodol
Lipiodol has specific affinity for
hepatoma cell and sticks to it
when administered trans-arterially into the tumour
05 B Cell lymphoma I131 Anti CD-20 Radioimmunotherapy. CD20 is
a surface pan B-cell antigen
expressed both on normal and
malignant B-cells
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Table 1 Gamma Imaging for Beta therapy
Imaging
Therapy
Recurrent ThyroidCancer
I-123, I-131 I-131
Neuroendocrine
tumour
I-123 MIBG I-131 MIBG
In-111 Octreotide Y-90 DOTATOC
Y-90 Otreother
Lu-177 Octreotide
In-111 Lanreotide Y-90 Lanreotide
Bone metastases Tc-99m MDP Sm-153 EDTMP
Re-186 HEDP
Non Hodgkin's
lymphoma
I-131 B1 Anti CD20* I-131 B1 Anti CD20
In-111 Retuximab* Y-90 Retuximab
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Ideal
Ideal Ra
diotherapeuticRa
diotherapeutic AgentAgent
The agent must accumulate at the site where tissue
destruction is required. The ideal radiotherapy agent
will show rapid accumulation of the activity at the
target site
The agent must be selective for the target tissue and
excluded from healthy tissue and organs, rapidly
cleared from the blood and rapidly excreted if not
bound to the target
The destructive action of the radionuclide must be
restricted to the target tissue following targeting
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TANTANG AN D AL AM R ADIOTER API
The ideal radiotherapy agent does not exist, ´magic
bulletsµ such as antibodies for delivery of curative
radiation to tumors have no lived up to expectation There is no ideal radio-nuclides. The beta emitters have
ranges of 1 to 12 mm in tissue, while the typical cell is in
the order of 10 µm
Alpha emitters have a more suitable ranges, but
carriers for alpha emitters are not currently reliable
enough for selective therapy.
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Terima kasih.