Nuclear Medicine2

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Dalam Bidang Kedokteran



Pemanfaatan Radioisotop / Senyawa

Bertanda

Sejarah dan Perkembangan Kedokteran

Nuklir

Prospek Perkembangan dalam KedokteranNuklir

Manajemen Pengobatan Kanker



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



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.



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



Evolving Paradigm in Medicine

Imaging

Anatomy Biochemical

Therapy

Systemic Targeted



New radiocompounds

New instruments and procedures

New approaches for old procedures

Kecenderungan Pengembangan Saat Ini



Manajemen Pengobatan Kanker

1. Diagnosis

2. Penentuan Keparahan dan Stadium Kanker3. Memonitor Terapi

4. Prognosis

5. R

adioterapi



1. Diagnosis

y Radiofarmaka untuk diagnosis

y Peralatan imagingy Modalitas non nuklir sebagai komplemen



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



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



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



Osteomyelitis and peritoneal tb



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.



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 isvery important

Accuracy of about 70-80%, but not accurate enough for distinguishing an aseptically loosened prosthesis from an infectedone (Palestro & Torres 1997)



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)



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



POSITRON EMISSION TOMOGR APHY

Siklotron

Synthesizer Module

Camera/Scanner

Komponen-komponen PET



PET/CT



PET-CT SCANNER

F-18 FDG PETCT



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



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



SPECT



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



Penentuan Keparahan dan Stadium Kanker

Diagnosis

Terlokalisasi Metastatis

Operasi atau Terapi

Radioterapi Sistemik



Staging Cancer

Specific OrganImaging

Whole body

Conventional PET



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



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.



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.



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.



Before treatment

Lymphoma staging

After the 2nd cycle

& effect of therapy



TERAPI RADIONUKLID A

´ Non-invasive

´ Invasive

´ Exploit the physiology unique to an organ ora neoplasm

´ Mechanical delivery



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



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



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



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.



Terima kasih.

Nuclear Medicine2

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