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Thyroid Cancer • Tumor Marker • Neuroblastoma • Bone Pain Palliation • Keloid - Heamangioma

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Thyroid Cancer • Tumor Marker • Neuroblastoma • Bone Pain Palliation • Keloid - Heamangioma Webinar Internal Bapeten, Rabu, 9 September 2020 Perkembangan Modalitas dan Layanan Kedokteran Nuklir Terkini Nasional dan International A. Hussein S. Kartamihardja Department of Nuclear Medicine and Molecular imaging Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin General Hospital Nuclear Medicine is defined as a medical specialty which uses the nuclear properties of matter to investigate physiology and anatomy, diagnosis diseases, and to treat with unsealed sources of radionuclide. (IAEA/WHO, 1988). What the different between Nuclear Medicine and Radiology • Physiology, molecular • Anatomy • Nuclear properties • Peripheral properties (x-rays) (gamma, beta, alpha) • Closed source • Open source • Transmissions • Emissions • External radiations (for • Radionuclide therapy treatment purpose) (internal radiations, etc) X-ray CT MR Nuclear Medicine IN-VITRO IMAGING THERAPHY (RIA/IRMA) DIAGNOSTICS Malignant - Benign • Hyperthyroidism • Thyroid Hormones • Thyroid Cancer • Tumor Marker • Neuroblastoma • Bone Pain Palliation • Keloid - heamangioma Nuclear Medicine Services left to right: Henri Becquerel, Marie Sklodowska Curie, Georg de Hevesy, Ernest Lawrence and Benadict Cassen. Hal Anger, David Kuhl, Gerd Muehllehner, Ron Jaszczak and Bruce Hasegawa. Gordon Brownell, Michael Phelps, Michael Ter- Pogossian, David Townsend and Ron Nutt. HISTORICAL MILESTONE OF NUCLEAR MEDICINE Some of the many scientists who have contributed to Nuclear Medicine. The three pillars of nuclear medicine Man Powers Instrumentations • Multidiciplinary • Gamma Cameras sklill • SPECT/CT • PET/CT • PET/MR Radiopharmaceutical • Reactor; Generator • Cyclotrone FreeThe Gear Future System Slides Trends for PowerPoint in Nuclear Medicine Radioisotopes 2 4 Service Equipments 1 Provision LOOKING AHEAD Radiopharmaceuticals 5 FreeThe Gear Future System Slides Trends for PowerPoint in Nuclear Medicine Radiotracers 1 2 LOOKING AHEAD Equipments Clinical 3 FreeThe Gear Future System Slides Trends for PowerPoint in Nuclear Medicine 1 Demand and Supply • NM Study : 40 m/year • Tc-99m: 80% • Radioisotopes demand : increased 5%/yr Radioisotopes 2 Initiatives • Market had substantially restructured following supply crisis 4 PET Tracers • Limited Radioisotop Production 99mTc- Generator Gallium-68 Generator Cyclotron Reactor Radioisotopes Strontium-90 Holmium-166 Pain relief 90 Sr 166 225 Indium-111 Ho Ac Targeted Diagnostic 188Re Thallium-201 Rhenium-188 32P Heart Health Iodine-131 Phosphore-32 Versatile Keloid Haemangioma Radioiodine Xenon-133 Luthetium-177 Breathing Easier 123 153Sm I Teranostic Samarium-153 Isotope Cancer therapy and Pain Relief 177Lu Yttrium-90 Liver Cancer and Technetium-99m radiosynovectomy The most widely used Gallum-67 isotope in the world Infection/Cancer Detection PET Tracer Flour-18 The most widely used PET tracer used in the world for cancer detection Amonium-13 Cancer Oxygen-15 82Rb Cardiac blood Rubidium-82 flow Myocardial perfusion Carbon-11 Gallum-68 Cancer 99mTc like Isotope for PET Targeted Diagnostic FreeThe Gear Future System Slides Trends for PowerPoint in Nuclear Medical Imaging 1 Multimodality Tracers Radiopharma • Tracers offering dual imaging ceuticals • Tc-99m colloid and stain blue 2 Targeted therapy • PSMA Ga-68 SIRT Y-90 • DOTA Lu-177 • PRRT • Targeted alpha therapy (BNCT) 4 Future Personalized Medicine • Molecular genetic imaging • Monitoring diff cellular process (PET) • Dynamic imaging of molecular and cell Ideal Radiopharmaceutical Properties for Diagnosis Pure gamma emitter Energy of Gamma Rays Ideal: 100-250 keV Short half-life isotope Localization only in Ideally1.5 times the tissue desired duration of the diagnostic procedure High Target to Non Easy preparation and target Ratio QC Economy price Availability Ideal Radiopharmaceutical Properties for Treatment Pure beta or alpha particle High or medium Energy > 1 MeV Relatively long half-life Localization only in isotope, ideally a couple tissue desired day High Target to Non Easy preparation and target Ratio QC Economy price Availability Radiopharmaceuticals No Radiopharmaceuticals Example 1 Ready to use I-123 Capsule; I-131 Hippuran; Ga-67 citrate; Tl-201 chloride; Xe-133 gas; Tc-99m pertechnetate 2 Instant Tc-99m kit DTPA; MDP; GH; MAA; PYP; Tetrofosmin, MIBI, MAG3; Sulfur colloid 3 Requiring significant Cr-51; Tc-99m RBC; Tc-99m WBC; manipulation 4 Short half life (Cyclotron) F-18; C-11 • Cerebrovascular disease • Thyroid Scan ’ • Alzheimer s disease • Thyroid Uptake • Schizophrenia, Epilepsy • Neonatal hypothyroidis • Neurotransmitter study • Myocardial Perfusion • Sciintimammography • Viability Study risk • Sentinel node detection stratification • Neuroreceptor imaging • Prevention of restenosis • V/Q Scan -- PE • Cardiac function 99m • Regional lung function Tc • Oesophageal TT • Hepatobiliary scan • Gastric emptying time • G-E reflux • Cystography • Renography • GFR • ERPF • Testicular scan • Renal scan • Flebography Whole body scanning • Venography •Bone scan • Lymphoscintigrapy •PET •Infection scan Well Differentiated Thyroid Carcinoma 131I POST OP; PRE 131I Rx 1 year later 131I 123I 99mTc 201Tl Ischemia “Gate Keeper” CA Infarction 18F 32P Phosphore-32 Keloid Haemangioma KELOID TREATMENT POST-TREATMENT PRE-TREATMENT Theranostics 2012, 2(5) 442 ence with such a condition). No significant hemato- and both showed a good clinical and objective thera- toxicity was observed in the two patients on dialyses py repsonse.22 Fig. 4: The Bad Berka Dose protocol – Analysis of regions of interest around whole body, tumor and normal organs in anterior and posterior planar whole body post-therapy (Lu-177 DOTA-somatostatin analogs) scans at 5 time intervals (A), determination of time activity curves in anterior and posterior scans (B) and using the geometric mean, fitting of the time-activity curves to an exponential function to obtain the residence time of the radiopharmaceutical in the region of interest. 90Y Yttrium-90 Fig. 5: VIPoma patient with Verner Morrison syndrome (severe watery diarrhoea, hypokalemia), high dose octreotide (Sandostatin LAR) prior to PRRNT. After administration of one single cycle of 5 GBq Y-90 DOTATATE, there was no need of octreotide after 3 months, 15 kg weight gain and significant reduction of tumor burden (partial remission. After follow up of 1 year, the liver and kidney functions were normal and only single liver metastasis remained. Follow-up of 2 years after 3 PRRNT cycles Response NETs of non-pancreatic Pancreatic hNETsttp://ww (wpNETs.thno.org) Complete/partial and minor 48% 52% remission Stabilized Disease 45% 39% RP Baum. 2012; 2(5):437-447. doi: 10.7150/thno.3645 68Ga RP Baum. 2012; 2(5):437-447. doi: 10.7150/thno.3645 Molecular Radiation Treatment Planning (MRTP) 18F- FDG DVH of PTV Baum RP et al. SNM 2000 68Ga- DOTA TATE Activated Macrophage somatostatin receptor-2 (SSTR-2) expression 68Ga-DOTATATE binds to SSTR-2 : High risk plaque detection Detect Inflammation and angiogenesis 68Ga- PSMA The 67-year-old patient had undergone previous radiotherapy of the prostate due to carcinoma and had received androgen therapy since 2002. The patient presented with a continuous increase of PSA values (from 1 ng/ml in 2002 to 7.4 ng/ml in May 2011) The Future Trends in Nuclear Medicine Imaging • SPECT/PET-CT aligned to anatomical PET SPECT Equipments /CT information without the use of external /CT markers or internal landmarks. • Find the design of different geometries and various 2 • The design of a prototype small detector technologies of Multimo animal PET PET SPECT and PET scanners dality /MR scanner 1 PET/MR more challenging • Systems are being Hybrid • Function and Structure designed for “low cost” Imaging • Blurred boundaries and very high- SPECT • Efficient /MR resolution • PET has become of more interest for clinical practice The Camera Rectilinear Scanner Planar Gamma Camera Double Head SPECT Camera PET/CT – PET/MR SPECT/CT Molecular Pathology Preclinical Imaging • Ligands, Targets • Animal PET/CT, PET/MRI, Digitalization of images • SPECT/CT • Data analysis • Gene analysis THERANOSTICS Molecular Imaging Molecular Therapy • PET/CT, PET/MRI • 4D-dosimetry • Novel tracers • Medicial physics • Clinical studies • Clinical studies • Multicenter trials PATIENTS TREATMENT PARADIGM Breaking the cycle Predictable Observation Test Action Response Trial and error medicine One-medicine-fits-all • Trial and error medicine Personalized Personalized • One-medicine-fits-all Medicine Health Care Targeted Therapy -Thera(g)nostics “THERAGNOSTICS” The combination of a diagnostic tool that helps to define the right therapeutic tool for a specific disease Easy to apply and to understand in Nuclear Medicine an easy switch of the radionuclide from diagnostic to therapy on the same vector The most prominent and oldest application is radioiodine The concept of Personalized Medicine appeared 34 THERANOSTIC PAIRS The Key-Lock Principle Reporting Unit Tumor Specific Receptor Target Molecule Radionuclide • 68Ga (ligant) (Chelator) • 99mTc • 111In • 18FDG Cancer Cel Cytotoxic Unit Linker • 90Y 177 • Antibodies, • Lu 186, 188 • Minibodies, • Re • Aptamer • Antigent • Peptides • Transporters • Amino acids “See and Treat Concept” • Enzyme “Targeted Therapy” • Inhibitor 35 Targeted radionuclide therapy in theragnostic systems 68Ga-DOTATATE (somatostatin receptors) 177Lu-DOTATATE Lee and Li. AJR:197, August 2011 Theragnostics and Targeted Therapy • offering the right • with the right dose treatment • providing a • for the right more targeted patient
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