PEMANFAATAN RADIOISOTOP /

SENYAWA BERTANDA
Dalam Bidang Kedokteran
Pemanfaatan Radioisotop / Senyawa
Bertanda

 Sejarah dan Perkembangan Kedokteran

Nuklir
 Prospek Perkembangan dalam Kedokteran
Nuklir
 Manajemen Pengobatan Kanker
 Sejarah dan Perkembangan
Kedokteran Nuklir
 Kedokteran Nuklir merupakan cabang ilmu kedokteran yang menggunakan
sumber radiasi terbuka berasal dari disintegrasi inti radionuklida buatan,
untuk mempelajari perubahan fisiologi, anatomi dan biokimia, sehingga
dapat digunakan untuk tujuan diagnostik, terapi dan penelitian kedokteran.

 Pembangunan Reaktor di Oak Ridge, Tenesse, USA memicu cara pembuatan

radioisotop yang lebih murah

 1 Agustus 1945 : The Atomic Energy Act, US Congress memunculkan Atomic

Energy Commission.
 Undang-undang ini menandai dimulainya produksi radioisotop untuk keperluan
kedokteran pada reaktor di Oak Ridge
Awal Mula (kedokteran) Nuklir
Henri Becquerel (1852-1908) French Physicist discovered radioactivity in 1896

Wilhelm Röentgen (1845-1923) German physicist who discovered X-rays in 1895.

Pierre Curie (1859-1906) French physicist who, along with his wife Marie
Sklodowska Curie, isolated polonium and radium in 1898.
Marie Sklodowska Curie (1867-1934) The winner of two Nobel Prizes for her
achievements in physics and chemistry. achievements include the creation of a theory
of radioactivity and discovery of Radium and Poloneum

Revigorator . After its discovery by Marie and Pierre Curie in 1898, radium was
considered a "cure-all" until the early 1920s.

Georg Von Hevesey (1859-1906) Hungarian-Danish chemist who first used radioactive
tracers in 1923 to study biologic systems by tracking the flow of radioactive tracers from
plant roots to the leaves. Won the 1943 Nobel Prize in chemistry for developing
radioactive isotopes as laboratory tracers.

Ernest O. Lawrence (1901-1958) American physicist who won the 1939 Nobel Prize
in physics for the invention of the cyclotron.

Glenn T. Seaborg (1912-1999) and John J. Livingood . They first produced Iron-59 in
1937 using an advanced cyclotron. They also discovered I-131 in 1938.
 Nuclear Medicine:The Middle Years
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.
 PROSPEK PENGEMBANGAN BIDANG KEDOKTERAN NUKLIR

Radioisotopes
&Radiopharmaceuticals

Instrumentation Medical Dr
 PERKEMBANGAN PENGGUNAAN RADIOISOTOP
Di 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
Evolving Paradigm in Medicine

Imaging

Anatomy Biochemical

Systemic Targeted

Therapy
 Kecenderungan Pengembangan Saat Ini

g New radiocompounds
g New instruments and
procedures
g New approaches for old
procedures
Manajemen Pengobatan Kanker

1. Diagnosis
2. Penentuan Keparahan dan Stadium Kanker
3. Memonitor Terapi
4. Prognosis
5. Radioterapi
1. Diagnosis

Radiofarmaka untuk diagnosis

Peralatan imaging
Modalitas non nuklir sebagai komplemen
Radiofarmaka ideal untuk pencitraan
infection/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
 Diagnostic 99mTc-Radiopharmaceuticals
99m
Tc-HMPAO
99m
Tc-ECD
Tc-MIBI
99m
Thyroid Imaging
99m
Tc-Tetrofosmin 99m
NaTcO4

99m
Tc-MAA
99m
Tc-SC
99m
Tc- HIDA 99m Tc-MAG3
99m
Tc-EC
Tc-anti CEA
99m
99m
Tc-DTPA
“Carcino Embryonic 99m
Tc-HEDSPHA
Antigen”
 Tc-99m
Tc-99m ciprofloxacin
ciprofloxacin

 There
Thereare
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inflammationisisstill
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 Infecton,
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broad
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 Invitro
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infectoncan
canbe
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Osteomyelitis and peritoneal tb
 Tl-201/MIBI

 Scintimammografi:
 Pada wanita berumur 50 tahun ke bawah, glandular breasts umumya
ditemukan pada radiografi, menyebabkan kesalahan ukur 25--45%
pada x-ray mammografi
 Tc-99m Sestamibi lebih sensitif dan spesifik
 Malignant lesions in patients with palpable breast abnormality
suspected of breast cancer
 Suspected recurrent cancer following breast surgery

 Kanker Lain:
 Brain, bone, thyroid, lungs, soft tissue sarcomas and in low grade
lymphomas
 Of special note is the ability of Tl-201 or Sestamibi to help differentiate
post therapy changes from tumor recurrence.
Scintimammography
 BONE SCANNING

Abnormal Abnormal
Normal bone
scintigraphy

AP PA
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 is
very important
 Accuracy of about 70-80%, but not accurate enough for
distinguishing an aseptically loosened prosthesis from an infected
one (Palestro & Torres 1997)
 F-18 FDG
(deoxyglucose labelled with F-18)

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
527079 9/23/99 prosthesis
 NEW ERA OF DIAGNOSIS :
POSITRON EMISSION TOMOGRAPHY

 Ditemukan pada tahun 1973 oleh Michael E Phelps

 Merupakan metode visualisasi metabolisme tubuh
menggunakan radioisotop pemancar positron
 Pencitraan yang dihasilkan merupakan gambaran fungsi
organ tubuh
 Metode pencitraan tubuh yang lain (MRI atau CT) hanya
menggambarkan kelainan bentuk organ tubuh
POSITRON EMISSION TOMOGRAPHY
Komponen-komponen PET

Siklotron

Synthesizer Module

Camera/Scanner
PET/CT
PET-CT SCANNER

F-18 FDG PET CT

KELEBIHAN 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
NEW ERA OF DIAGNOSIS : 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 –
computed tomography (PET-CT) in oncology
 But relatively little focus on the clinical utility of
SPECT-CT
SPECT
CLINICAL APPLICATIONS OF SPECT/CT
 There are some instances where single photon-emitting
radiopharmaceuticals are predictably more sensitive and specific:

 Endocrine-related tumors that express somatostatin receptors

 The octreotide series of single 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
Penentuan Keparahan dan Stadium Kanker

Diagnosis

Terlokalisasi Metastatis

Operasi atau Terapi

Radioterapi Sistemik
Staging Cancer

 Specific Organ
Imaging
 Whole body
 Conventional
 PET
 Pemantauan Terapi

 Diagnosa Kedokteran Nuklir:

 Mendefinisikan tumor and menentukan ke
 Memonitor respon terapi dengan penentuan
perubahan ukuran tumor, termasuk marker-marker
tumor lainnya, selama dan sesudah terapi
 Memprediksi Prognosis
 3. Monitoring Therapy

 Most often the tumors:

 Spread in the form of two dimensional sheets, rather
than three dimensional structures
 Besides, using the structure based diagnostic
procedures:
 It is almost impossible to correctly distinguish viable tumor
from scar tissues, necrotic materials and granulation tissues
which are present in variable amount in and around a tumor
following its treatment with radiation or chemotherapeutic
agents.
 3. Monitoring Therapy

 Functional imaging using radionuclides

provides an excellent opportunity:
 to determine the response and identify presence of
viable tumor tissue during or following chemo or
radiotherapy
 thereby aiding the treating physician to take
decisions with respect to:
 continuation, modification or abandoning a particular
form of treatment.
Prognosis

g Differential uptake of radiolabeled compounds

may permit characterization of lesions which may
not be distinguishable at the histopathology
level.
g Uptake changes may provide the earliest
evidence of therapeutic response.
g Tc-99m lipophillic cations may allow to identify
patients with multi-drug resistant phenotypes.
Lymphoma staging & effect of therapy

Before treatment After the 2nd cycle

TERAPI RADIONUKLIDA

 Non-invasive
 Invasive
 Exploit the physiology unique to an organ or a
neoplasm
 Mechanical delivery
01 Thyroid I-131 Iodine is actively accumulated
metabolized in the thyroid
gland
02 Metastatic Bone Pain Sr-89, P-32, These are bone seeking radio-
Sm-153 EDTMP, pharmaceuticals, actively taken
Re-188 HEDP up by the sites of bone
metastases
03 Malignant I-131 MIBG These tumours preserve the
phoeochromo- unique ability to concentrate
cytoma and neuro- metaiodo-benzyleguanidine
endocrine tumours (MIBG)
04 Liver cancer I-131 Lipiodol, Lipiodol has specific affinity for
(Hepatocellular Re-188 Lipiodol hepatoma cell and sticks to it
carcinoma) 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
Table 1 Gamma Imaging for Beta therapy
Therapy
Imaging
Recurrent Thyroid I-123, I-131 I-131
Cancer
Neuroendocrine I-123 MIBG I-131 MIBG
tumour
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 I-131 B1 Anti CD20* I-131 B1 Anti CD20
lymphoma
In-111 Retuximab* Y-90 Retuximab
 Ideal Radiotherapeutic Agent
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
TANTANGAN DALAM RADIOTERAPI

 The ideal radiotherapy agent does not exist, “magic

bullets” 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.
 Current trends

g New radiocompounds
g New instruments and
procedures
g New approaches for old
procedures
Terima kasih.