nuclear medicine in indonesia 2015 -...

Nuclear Medicine in

Indonesia2015

School of Medicine Universitas PadjadjaranDr. Hasan Sadikin Hospital

Bandung

Johan S. MasjhurDept. of Nuclear Medicine and Molecular Imaging

STTN BATAN Yogya Sept 2015

Apakah itu Kedokteran Nuklir :

Cabang ilmu kedokteran yang menggunakan sumber radiasi terbuka berasal dari disintegrasi inti radionuklida buatan, untuk mempelajari perubahan fisiologi dan biokimia pada tingkat sel dan molekul, yang digunakan untuk tujuan diagnostik, terapi dan penelitian.

Kata kunci :- Sumber radiasi terbuka – disintegrasi inti radionuklida buatan- Perubahan fisiologi dan biokimia – sel dan molekul functional morphology- Diagnostik, terapi dan penelitian

SEMINAR NASIONAL XI SDM TEKNOLOGI NUKLIR YOGYAKARTA, 15 SEPTEMBER 2015 ISSN 1978-0176 ________________________

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Nuclear Medicine

Medical PhysicistsRadiopharmacists


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1965 :First atomic reactor in IndonesiaReactor Triga Mark 2000 – 2 MWBandung Atomic Center (Pusat Reaktor Atom Bandung)1967 :First Nuclear Medicine Service located in Bandung Atomic Center

Nuclear Era in Indonesia

1982: Kartini Reactor in Yogyakarta – 300 kW

1988 :Multipurpose Atomic Reactor “GA Siwabessy” in Jakarta

Historical Milestones “Nuclear Medicine Era in Indonesia”

* 1971 : The First Nuclear Medicine Department in IndonesiaDr. Hasan Sadikin Hospital School of Medicine Universitas PadjadjaranBandung - Indonesia


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NUCLEAR ERA IN INDONESIA

Prof. Dr. G.A. Siwabessy (1914-1982)Bapak Atom Indonesia

- 1954 : Direktur, Lembaga Tenaga Atom

- 1963-1965 : Dekan pertama FMIPA UI

- 1962 : Direktur Jenderal pertamaBadan Tenaga Atom Nasional;

- 1965 : Menteri Badan Tenaga Atom Nasional;

- 1966 – 1978 : Menteri Kesehatan

Prof. Dr. Achmad Baiquni (1923-1998)Fisikawan Atom Pertama Indonesia

1973 – 1984 Direktur Jenderal BATAN

IR. DJALI AHIMSADirektur JenderalBadan Tenaga Atom NasionalPeriode 1984 - 1996

IR. IYOS R. SUBKIDirektur JenderalBadan Tenaga Atom NasionalPeriode 1996 - 2002


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Prof. Dr. SutarmanKetua Umum PKBNI

1976 - 1984

Prof. Dr. DjokowoerjoSastradipradjaKetua Umum PKBNI1984 -1988

PE

RH

IMP

UNAN KEDOKTERANN

UK

LIR

I N D O N E S I A

Prof. Dr. Johan S. Masjhur, SpPD-KEMD, SpKNKetua Umum PKBNI 1988 -2004Ketua Umum PKNI 1988 - 2004

Dr. A. Hussein S. Kartamihardja, SpKNKetua Umum PKBNI/PKNI2004 - 2012

Dr. Trias Nugrahadi, SpKNKetua Umum PKBNI/PKNI

2012 - 2016

ORGANISASI PROFESI PKNI/PKBNI

PIONIR KEDOKTERAN NUKLIR DI INDONESIA

Prof.Dr. Sutarman Dr. LF Luhulima, SpOGRSP Pertamina FK Unpad / RSHS

Prof. Dr. Asmino Dr. Erie WidjajaFK Unair / RS Dr. Sutomo FKUI / RSCM

PE

RH

IMP

UNAN KEDOKTERAN

NU

KL

IR

I N D O N E S I A


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PIONIR KEDOKTERAN NUKLIR DI INDONESIA

Dr. Ruchijat Suwarno Dr. Subur Budiman Dr. Tenri AbengRSP Pertamina FKUI/RSCM FKUI/RSCM

Kol. Dr. Jusuf Dr. Subowo Dr. Kahar S.RSGS RSP Pertamina FKUI/RSCM

PE

RH

IMP

UNAN KEDOKTERANN

UK

LIR

I N D O N E S I A

Dr. Setiono Diran Dr. Bagaswoto Pudjomartono Dr. Gogot SuyitnoFK Unair/RSD Dr. Sutomo FK UGM/RS Prof.Dr. Sardjito FK UGM/RS Prof.Dr. Sardjito

Dr. Nifa Wahid Dr. Manufris Kasim Prof. Dr. Nursal AsbiranFK Unair/RSD Dr. Sutomo RS Jantung Harapan Kita FK Unand

Nuclear Cardiology Radioimmunoassay


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Tokoh Radiofarmasi Indonesia

Drs. Anhar Yunus Prof. Dr. Aang Hanafiah

Historical Milestones of “Nuclear Medicine Era in Indonesia”

1967 The first NM unit in Indonesia –

“Balai Kedokteran Nuklir”

at Bandung Reactor

1971moved to Dr.

Hasan SadikinHospital – Dept.

of Nuclear Medicine

1976The Indonesian

Society of Nuclear Medicine & Biology

1989The Indonesian

Society of Nuclear Medicine

1992The 5th Asia-Oceania Nuclear

Medicine and Biology Congress in Jakarta

1997Recognition of

NM as a medical specialty

1999 : # Center of Specialist Program : NM Physicians# National Referral Center for Nuclear Medicine at

Dr. Hasan Sadikin Hospital –Faculty of Medicine Universitas Padjadjaran Bandung


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Historical Milestones “Nuclear Medicine Era in Indonesia”

The 5th Asia Oceania Congress of Nuclear Medicine and Biology Jakarta, 26 – 30 October 1992.

2010 - ….New Era of Nuclear Medicine in Indonesia

PET/CT

RS Gading Pluit RS MRCCC Siloam

RS Kanker Dharmais RS Dr. Hasan Sadikin


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Manpower Development

First generation of nuclear medicine physicians : had their education and training

abroad

1999 – now :Education and training: “in house/local”

Dept. of Nuclear Medicine and Molecular ImagingFaculty of Medicine Universitas Padjadjaran

Dr. Hasan Sadikin Hospital Bandung

2015(September 2015)

In house/local NM physicians : 29NM Residents : 12

Education and Training Program for Technologists : NONE

Nuclear Medicine in Indonesia

…………………………..Tomorrow


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Do we need Nuclear Medicine ?

Key factors for a good Nuclear Medicine service !Challenges !

PAST PRESENT “FUTURE”

MolecularNM, PET, SPECT,

MRS, optical, PET/MRI

contrast-enhanced MRI/US/CT

Hybrid

PET/CT, SPECT/CT, PET/MR

Functional

angiography, doppler US, NM,

MRI, PET

Anatomic

plain films, CT, MRI, US

The evolution of diagnostic imaging


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Nuclear Medicine is a Bridge !

Molecular Medicine <Nuclear Medicine> Clinical Medicine

Basic Science Nuclear Medicine Medical Technology

Research Technology

PET-CT Scanner Dr. Ron Nutt and Dr. David Townsend

F-18 FDG PET CT


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Changing concept of medicineOrgan oriented Molecular oriented

Focus of interest :MetabolismImmunologyReceptor study (endocrine, tumor, and neurotransmitter)

Molecular Biology

Molecular Medicine

Molecular Nuclear Medicine

Molecular ImagingTargeted Therapy

Theranostics

Personalized Medicine

MOLECULAR MEDICINE

Pencitraan molekuler :visualisasi, karakterisasi dan pengukuran proses biologik pada tingkat molekuler dan seluler dari manusia atau makhluk hidup lain.

Task Force of the Molecular Imaging Center of Excellence of the Society of Nuclear Medicine


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MOLECULAR IMAGINGPENCITRAAN MOLEKULER

Pencitraan molekuler berawal pada teknik pencitraan radionuklida yang digunakan dalam prosedur kedokteran nuklir.

Kamera PET, single photon emission computed tomography (SPECT), dan kamera gamma planar telah sejak lama digunakan untuk mendeteksi probe bertanda radionuklida.


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Molecular imaging has its rootsin Nuclear Medicine ;and in many ways is a direct extension of Nuclear Medicine.

Through the use of state-of-the-art molecular and cell biology, we can nowbetter design molecular probes (tracers)that can target specific cellular/molecular events.We can also engineer cells so that they will specifically accumulate tracers of choice.

Pencitraan Molekuler

• Nuclear Medicine radiolabelled molecules

• Ultrasound sound

• Magnetic Resonance Imaging magnetism

• Optical Imaging light

PET/CT SPECT/CT

MR Spectroscopy

Optical Imaging

Targetedultrasound


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~90 % of clinical molecular imaging is PET and SPECT Optical, other modalities on the

horizon Nanoparticles, bacteria, new probes

used to image critical cancer processes (cell death, tumor proliferation, angiogenesis, hypoxia) on the horizon Reporter-probe pairs are being

generated for molecular-genetic imaging

MOLECULAR IMAGING IN ONCOLOGYPencitraan Molekuler dalam Onkologi


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S. Gambhir U. Mahmood

Nuclear: [18F]FHBG for tracking T cells

Optical: Activatable fluorescencefor intestinal adenoma

P. Van Zijl

MR: Amide proton transfer imaging to assess brain tumor characteristics

Nuclear: PSMA imaging for prostate cancer J. Babich

The Evolving Role of Nuclear Medicine in Oncology

See & Treat

See:Tag gamma-emitter to molecular agent, inject in patient, goes to the target molecule, make images.

Treat:Add beta-emitter to molecular agent, inject, goes to the target molecule and delivers the therapy.

PET / CT Camera

Clinical application in Oncology

- staging and location of lesions - evaluation and monitoring - viability versus fibrosis

Cancer :lung, breast, colorectal, lymphoma, melanoma,head and neck, thyroid, neuroendocrine


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Courtesy Dr. Abdel-Dayem, St. Vincent’s, NY

Lung CaSee

• Measure efficacy of Rx

• Results 6 hrs after 1st treatment

• Avoid unsuccessful Rx

Treat• Add Re-188 guided missile

• Boost effects of initial Rx

• Eliminate debilitating effects of ChemoRx

48h Post ChemoRx

Theseus Tc-99m ApomateAnnexin V

I-131 : Beta & Gamma radiation

Iodine goes to thyroid gland Na I-131 Given to Thyroid Ca patient Thyroid Ca disappeared

o Adjuvant

o Remnant Ablation

o Therapy

Well Differentiated Thyroid Carcinoma


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Ca Thyroid

123I Total Body ScanOctober 2002 April 2003

The image is actually two sets of before-and-after PET scans of two patients. One patient was treated with (a) Iodine-131 tositumomab(Bexxar®). The other received (b) Yttrium-90 ibritumomab tiuxetan(Zevalin®). The PET images reveal that both patients showed no metabolically active NHL as early as three months after treatment.

Courtesy of : A. Iagaru; E. Mittra, M. Goris; 2009

before after before after(a) (b)

Non-Hodgkins Lymphoma


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In-111 octreotide (penteterotide) study demonstrating uptake in a primary gastrinoma (arrow on anterior image) and a liver metastasis (arrow on posterior image).

(Source : Murray and Brooks, 2000).

I-123 MIBG study demonstrating high uptake in a left adrenalphaeochromocytoma.

(Source : Murray and Brooks, 2000)

Screening Patients with SSR‐ImagingNormal distribution


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Imaging gene therapy with PET in unilateral MPTP monkey model ofParkinson’s. Dopamine synthesis was imaged with aromatic amino acid decarboxylase substrate, meta-[18F] fluorotyrosine. (Left) Normal dopamine synthesis in striatum. (Center) Unilateral dopamine MPTP-induced deficit (arrow) before gene therapy. (Right) Restoration of dopamine synthesis (arrow) after gene therapy using a virus that contained the aromatic amino acid decarboylase gene. (Courtesy of K. Baukiewicz, 2000).

MOLECULAR IMAGING IN NEUROSAINS

Pencitraan Molekuler dalam Neurosains


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(Phelps ME, 2000)

MOLECULARIMAGING IN CARDIOLOGY

Pencitraan Molekuler dalam Kardiologi


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Adenosine 82Rb stress-rest study. 82Rb allows high-quality images. This study demonstrates normal myocardial perfusion at stress and rest with homogeneous uptake throughout.

Myocardial Blood Flow

Stress/rest Tc 99m sestamibi short-axis, vertical long-axis, and horizontal long-axis left ventricular

images showing a severe, fixed myocardial perfusion defect in the inferior wall, consistent with

previous infarct or myocardial necrosis.

Cardiac viability study. Top rows (A) represent FDG study; bottom rows (B) represent 82Rb perfusion examination. Short-axis images demonstrate a large perfusion defect in the lateral segments (white arrow). There is uptake of FDG in these segments (yellow arrow), indicating viable myocardium. Horizontal long-axis images demonstrate that the perfusion defect involves the apex as well as the lateral wall; all segments are viable as indicated by FDG uptake.(Weissman G and Sinusas AJ. 2011)

PET patterns of myocardial viability. Left panel, Concordant reductions in myocardial perfusion (rubidium 82) and glucose metabolism (18FDG), reflecting myocardial infarction. Right panel, Preserved glucose metabolism (18FDG) in a territory with decreased myocardial perfusion (rubidium 82), reflecting complete tissue viability.

(From Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary Artery disease. Circulation 2007; 115:1464-1480.)


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TARGETED RADIONUCLIDE THERAPY

Terapi Radionuklida Bersasaran


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Targeted therapy in Nuclear Medicine

Radioiodine in Thyroid Carcinoma :• rhTSH-aided • Redifferentiating agents : retinoid acid

Radioimmunotherapy with mAbs : B-cell lymphoma, follicular lymphoma

* Y-90 ibritumomab (Zevalin®, IDEC Pharmaceuticals and Schering AG)

* I-131 tositumomab (Bexxar®, GSK Philadelphia PA)

Radiolabelled MIBG : Neuroectodermal tumors (neuroblastoma, pheochromocytoma, paraganglioma, medullary thyroid carcinoma, carcinoid tumors,Merkelcell tumors of the skin)

* I-131 MIBG

Targeted therapy in Nuclear Medicine

Peptide Receptor Radionuclide Therapy (PRRT)Neuroendocrine tumors

Radiolabeled somatostatin analogues :* In-111 DTPA octreotide* Y-90-DOTA, Tyr3 –octreotide (phase I-II clinical trials)* Lu-177-DOTA, Tyr3-octreotate

Radionuclide therapy of liver tumors and metastases

* I-131 lipiodol (Lipiocis®, Schering S.A., Berlin, Germany)

* Re-188 lipiodol (no high energy gamma)


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THERANOSTICS


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Theranostics

Theranostics = Therapy + Diagnostics

The diagnostics is linked to the therapeutic substance to select patients who would be suitable for treatment by a particular drug.

Non‐Hodgkin’s Lymphoma

Specific‐binding to a tumor‐associated antigen (i.e. CD20)

Diagnostic TherapyIbritumomab ,tiuxetan

111In‐DTPA‐Ibritomomab 90Y‐DTPA‐Ibritomoma

Currentapproach

In vitromarkers

Diagnostic (anatomic) imaging, biopsies

symptomsdiagnosis

• Non-personalizedmedication

• Chemotherapy• Radiotherapy• Surgery

Followup

Molecular ImagingMolecular Imaging

MolecularMedicineapproach

Molecular Therapy

Molecular Therapy

DNAscreens

Proteinscreens

Monitor TreatmentMonitor Treatment

EarlierPersonalizedIntegratedEfficient

Diseaseprogression

Mortality& costs

Geneticpredis-position

First cellmutations

Asympto-maticdisease

Diseased cells release biologicalmarkers

First symptoms/manifestation

Diseaseproliferation

Environmental trigger


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TreatmentDiagnosis/P Prognosis

Physician

Interaction

Triggers toAdvance to Physicians

Self-Directed Healthcare

ActivitiesPatient

Current Healthcare Value Chain

SymptomsPeriodic checkupsSelf‐diagnosis

Diet, Exercises, Self‐monitoring

Hospital visitVisit healthcare provider facilities

At point of careCentral labsImaging facilities

MedicineSurgeryOther treatment

TreatmentPrognosisDiagnosisPhysician

Interaction

TriggersAdvance

to

Physicians

Management of

PredisposedRisk

DiseaseP

PredispositionAssessment

Individual

Genetic testing Other molecular testing

Preemptive therapies Monitoring of risk development

Early diagnosis Molecular level diagnosis

Molecular level tests for staging and progression prediction

More effective and stratified medicine

Future Healthcare Value Chain

Changing Healthcare Value Chain

Sean Xinghua Hu, et al. BioTechniques , 2005, 29(5), doi 10.2144/000112048

KEDOKTERAN NUKLIR DI INDONESIA


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Do we need nuclear medicine in Indonesia ?

* Changing pattern of diseases in Indonesia :Cerebrocardiovascular diseasesDegenerative and metabolic diseasesCancer

* Basic and applied research in medicine and allied sciences biomedical research

Significant role of NM technology

Indonesia

•17.000 islands•225 million population•52 state universities, and more than 100 private universities•100 state owned hospitals, and more than 200 private hospitals•18 state owned + 17 private teaching hospitals•18 state owned + 17 private Schools of Medicine

•Only 14 nuclear medicine centers (5 inactive)

Potential market for health sector business including Nuclear Medicine


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Nuclear medicine in Indonesia

1. Cipto Mangunkusumo (SPECT/CT)2. Pertamina (SPECT)3. Gatot Subroto (SPECT)4. Kanker Dharmais (SPECT/CT, PET/CT)5. Jantung Harapan Kita (SPECT)6. Gading Pluit (PET/CT)7. MRC Cancer Center (SPECT, PET/CT)

Kariadi GH (SPECT)(Semarang)

Soetomo GH (SPECT)(Surabaya)

Sardjito GH (SPECT)(Jogyakarta)

Hasan Sadikin GH(Bandung)

SPECTSPECT/CT

PET/CT

M. Djamil GH (SPECT)(Padang)

Adam Malik GH (SPECT)(Medan)

PERKEMBANGAN KEDOKTERAN NUKLIR DI INDONESIA SANGAT LAMBAT

1980-an : 14 unit kedokteran nuklir

2013

Active : RSHS, RSCM, RSP Pertamina, RS Gatot Subroto, RS Kanker Dharmais, RS MRCCC, RS Gading

Pluit, RS Dr. Kariadi Semi-active : RS Dr. M. Djamil, RS. Adam Malik,

RSD Dr.Sutomo, RS Dr. Sardjito, RS Jantung Harapan Kita

Non-active : RS Dr. Wahidin


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Nuclear phobia dan mis-persepsi

Investasi tinggi, bukan prioritas

dalam pelayanankesehatan

Minat kurangdalam ilmu

kedokteran nuklir

“bila yang ingin saudara raih dengan menjadi dokter adalah tingkat kesejahteraan yang setinggi-tingginya, maka

kedokteran nuklir agaknya bukan bidang yang tepat untuk itu; namun bila saudara memiliki sedikit idealisme dan minat

dalam pengembangan ilmu dan teknologi kedokteran,kedokteran nuklir dapat saudara jadikan salah

satu opsi pengembangan karier saudara kelak”

Quality Management Audits in Nuclear Medicine Practices. IAEA 2008.


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Nuclear Medicine as a medical specialty facessignificant challenges due to the intersection withRadiology, which has accelerated since theintroduction of hybrid imaging and the evolution ofMolecular Imaging;

These pressures are being felt after decades ofstrong growth for Nuclear Medicine, particularly inNuclear Cardiology and PET/CT. The emergence ofMolecular Imaging with new radiopharmaceuticalsand new technologies is likely to result in continuedgrowth in the coming decades.

SNM, 2011

Challenges

OPPORTUNITIES

• Nuclear Medicine has had decades of stronggrowth, particularly in Nuclear Cardiologyand Oncology (PET/CT);

• The emergence of Molecular Imaging withnew radiopharmaceuticals and new technologiesis likely to result in continued growth in thecoming decades.

SNM, 2011


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Key factors for a good Nuclear Medicine and Molecular Imaging services in Indonesia

1. Supply and logistics of radiopharmaceuticalsNM highly depends on good supply and logistics of radiopharmaceuticals;

2. Instrumentations and supporting facilitiesUpdating new technologies;

3. Manpower : NM physicians, Radiopharmacists, Medical Technologists, Medical PhysicistsManpower development;

4. Appreciation to NM and MI servicesMedical community “Nuclear phobia”;

5. Accessibility to NM and MI services2013 : active centers only in Jakarta and Bandung.

Nuclear medicine bridges basic medical sciences

and clinical medicine, and plays an important role in

biomedical research.

Nuclear Medicine has an unique contribution in the management of diseases.

The future of NM in Indonesia depends on the

good acceptance and appreciation of public authority and medical

community, and also good supporting facilities.


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MIMPIKU 15 TAHUN YANG LALU. FK UNPAD/RSHS MEMILIKI PET/CT CAMERA

“Medicine has moved from whole body to organs to tissues to cells and now to molecules. We are indeed in a revolutionary time in the history of medicine”

Henry N. Wagner, Jr., 2008


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Molecular Nuclear Medicine:

We are small, but very focused !


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Terima kasih

Hatur nuhun

Matur nuwun

Einstein and me ........


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