RADIOISOTOPES in MEDICINE:

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RADIOISOTOPES in MEDICINE: Requirements - Production - Application and future prospectives 2 Imaging with Radiotracers Gerd-Jürgen BEYER Prof.Dr.rer.nat.

1 RADIOISOTOPES in MEDICINE: Requirements - Production - Application and future prospectives 2 Imaging with Radiotracers Gerd-Jürgen BEYER Prof.Dr.rer.nat.habil.(i.R.) Geneva, Switzerland THIRD INTERNATIONAL SUMMER STUDENT SCHOOL NUCLEAR PHYSICS METHODS AND ACCELERATORS IN BIOLOGY AND MEDICINE Dubna, July 01-11, 2005

2 THE TRACER PRINCIPLE 1923 G.V.Hevesy: The Absorption and Translocation of Lead (ThB) by Plants [ThB = 212 Pb] Biochem.J. 17, 439 (1923) Measurements of the tracer s Radioactivity provided thousand fold increases in sensitivity and accuracy over existing chemical assays. The foundation and basic rationale of much of Hevesy visualized that a radioactive atom might be used as a representative tracer of stable atoms of the same element whenever and wherever it accompanied them in biological systems Nobel Prize Chemistry G.V.HEVESY the father of Nuclear Medicine

3 NUCLEAR MEDICINE = in vivo APPLICATION of RADIOTRACERS 1923 First tracer study with 210 Pb/ 210 Bi G.Hevesy Bi arm-to-arm circulation time, H.Blumgart P renewal of mineral constituents of bone, O.Chieivitz & G.Hevesy 1937 dynamics of sodium transport in vivo, J.G.Hamilton I, thyroid physiology, R.Hertzs, A.Roberts, R.Evans I discovered by G.T.Seeborg, 1939 first diagnostic use J.G.Hamilton et al I Fluorescine, I HSA, I-rose bengale & hippurane, Mo- 99m Tc generator (1960 first sale), 133 Xe for lung ventilation Ga accumulation in cancer, C.L.Edwards 1970 Instant KIT s for 99m Tc Tl, 123 I, 111 In, many other isotopes and tracer compounds 1978 first 18 FDG PET scan 11 million individuals receive every year a radiotracer for diag nosis

4 ISOTOPES IN MEDICINE DIAGNOSIS THERAPY in vitro in vivo internal external 14 C 3 H 125 I others 99 Mo- 99m Tc 201 Tl 123 I 111 In 67 Ga 81 Rb- 81m Kr others ß + emitters for PET 18 F, 11 C, 13 N, 15 O 86 Y, 124 I 68 Ge- 68 Ga 82 Sr- 82 Rb systemic sources tele radio 131 I, 90 Y 153 Sm, 186 Re 188 W- 188 Re 166 Ho, 177 Lu, others α-emitters: 225 Ac- 213 Bi 211 At, 223 Ra 149 Tb e - -emitters: 125 I sealed sources 192 Ir, 182 Ta, 137 Cs many others needles for brachytherapy: 103 Pd, 125 I many others stants 32 P and others seeds 90 Sr or 90 Y, others applicators 137 Cs, others 60 Co gamma knife 137 Cs blood cell irradiation G.J.BEYER, HUG Geneva, 2002

5 ISOTOPES in MEDICINE Application Requirement Isotope DIAGNOSIS in vitro DIAGNOSIS In vivo SPECT DIAGNOSIS in vivo PET T ½ = long biogenic behavior single photons no particles biogenic behavior T ½ = moderate ß + -decay mode biogenic elements T ½ = short 3 H, 14 C 125 I 99m Tc, 123 I, 111 In, 201 Tl, 11 C, 13 N, 15 O, 18 F

6 Diagnostic in vitro RIA Rosalyn S.YALOW S.A.BERSON Nobel Prize 1977 Introduced the radioimmunoassay (RIA) assay for insulin based on the principle of competitive binding by antibody of natural and radioactive labeled hormone)

7 ISOTOPES in MEDICINE Application Requirement Isotope DIAGNOSIS In vitro DIAGNOSIS In vivo SPECT DIAGNOSIS in vivo PET T ½ = long biogenic behavior single photons no particles biogenic behavior T ½ = moderate ß + -decay mode biogenic elements T ½ = short 3 H, 14 C 125 I 99m Tc, 123 I, 111 In, 201 Tl, 11 C, 13 N, 15 O, 18 F

8 Photo published 1942 J.G.Hamilton, M.H.Soley: Studies of iodine metabolism by thyroid in situ 1940, Am.J.Physiol. 131, 135 Kidney Isotope Nephrogram

9 signals x +, x -, y +, y - GAMMA CAMERA electronics Pb shielding PM tubes H.O.ANGER 1958 light gide window NaI-Detector collimator Planar scintigram Scan Thyroid normal B.CASSEN SCANNER Pre-amplifier PM-tube Pb-shielding NaI-Detector Collimator Object

10 SPECT Single Photon Emission Computed Tomography m Tc DMPE

11 Nuclear Medicine Instrumentation Point sensitive stationary moving Point collimator single detector GM / NaI -PM NaI-PM Probe Scanner DETECTOR are Place sensitive stationary moving multi-hole collimatuers NaI + many PM s single head 1-3 heads γ-camera SPECT combined with / without septa Multi-ring systems Block detectors BGO PET 67 GaCIT 99m Tc DMPE 1 D 2 D dynamic static 2 D 3 D dynamic dynamic 2 D and 3 D dyn. & quantitative

12 Modern SPET Cameras (GE Medical Systems)

13 NUCLEAR MEDICINE 2005 DIAGNOSIS SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY) increase of diagnostic value new radiopharmaceuticals dedicated instrumentation & quantification Molecular PET AS RESEARCH TOOL in vivo biochemistry Gene expression Clinical research PET Imaging AS CLINICAL TOOL Oncology Reimbursement of FDG-studies Neurology Cardiology Multi -modality Imaging combined SPECT -PET (image of the year at the 46.SNM) Function and morphology ( PET CT ) THERAPIE NEW APPROACHES IN RADIONUCLIDE THERAPY bio-selective antibodies (mab = monoclonal antibodies) bio-specific peptides (Octreotides, others) gene therapy free chelators like EDTMP Lyposomes Nanoparticles NEW RADIONUCLIDES for THERAPY α-therapy & AUGER THERAPY PET FOR IN VIVO DOSIMETRY β - emitters α-emitters metallic positron emitters labelled drugs dose localization G.BEYER (HUG, Geneva, 2005)

14 141 kev photons - the strength of 99m Tc

15 99m TcO % NaCl solution + KIT s many different 99m Tc-tracer for imaging of many different organ and tissue functions

16 Tc-HMPAO Tc-MIBI Tc-O12 99m Tc Perfusion Tracers Tc-NOEt Tc-P53 Tc-BATO

17 HEART Perfusion Ventilation study LUNG Function Perfusion Study 99m Tc TRACER Examples BONE metabolic activity

18 NUCLEAR MEDICINE 2005 DIAGNOSIS SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY) increase of diagnostic value new radiopharmaceuticals dedicated instrumentation & quantification PET AS RESEARCH TOOL Molecular in vivo biochemistry Gene expression Clinical research PET AS CLINICAL TOOL Multi Oncology Reimbursement of FDG-studies Neurology Cardiology -modality Imaging combined SPECT -PET (image of the year at the 46.SNM) Function and morphology ( PET CT ) THERAPIE NEW APPROACHES IN RADIONUCLIDE THERAPY bio-selective antibodies (mab = monoclonal antibodies) bio-specific peptides (Octreotides, others) gene therapy free chelators like EDTMP Lyposomes Nanoparticles NEW RADIONUCLIDES for THERAPY α-therapy & AUGER THERAPY PET FOR IN VIVO DOSIMETRY β - emitters α-emitters metallic positron emitters labelled drugs dose localization G.BEYER (HUG, Geneva, 2005)

Nuclear Medicine Instrumentation Point sensitive stationary moving

DETECTOR are Place sensitive stationary moving multi-hole collimatuers

without septa Multi-ring systems Block detectors BGO PET 67 GaCIT 99m

19 Nuclear Medicine Instrumentation Point sensitive stationary moving Point collimator single detector GM / NaI -PM NaI-PM Probe Scanner DETECTOR are Place sensitive stationary moving multi-hole collimatuers NaI + many PM s single head 1-3 heads γ-camera SPECT combined with / without septa Multi-ring systems Block detectors BGO PET 67 GaCIT 99m Tc DMPE 1 D 2 D dynamic static 2 D 3 D dynamic dynamic 2 D and 3 D dyn. & quantitative

20 PET = Positron Emission Tomography 0.51 MeV 0.51 MeV

21 FDG-PET Dementia - Alzheimer s

23 FDG-PET Melanoma therapy control before after

CANCER About 1 000 000 new cancer cases per year in EU 58 % local disease, 42 % generalized HOW: 45 % cured (5 year survival) just beginning of 22 % surgery alone 12 %

24 CANCER About new cancer cases per year in EU 58 % local disease, 42 % generalized HOW: 45 % cured (5 year survival) just beginning of 22 % surgery alone 12 % radiation therapy 6 % combination surgery + radiation 5 % chemo-therapy systemic radionuclide therapy expose cancer cells or cancer tissue with sufficient radiation doses?

p.i. ECAT ACCEL 50 year-old male with colon CA 91 kg, 183 cm, 720 MBq FDG, 162 min p.i. Emission scan

25 3D whole-body PET ECAT HR+ 25 year-old male with Melanoma, 71 kg, 178 cm, 625 MBq FDG, 45 min p.i. ECAT ACCEL 50 year-old male with colon CA 91 kg, 183 cm, 720 MBq FDG, 162 min p.i. Emission scan time: 54 min Transmission scan time: 18 min Data courtesy of Kettering Memorial Hospital, Kettering, USA Emission scan time: 27 min Transmission scan time: 18 min Data courtesy of NC PET Imaging Center, Sacramento, USA

26 The FIRST FDG SYNTHESIZER J. Fowler, BNL

27 SYNTHESIS OF [ 18 F]FDG PRODUCT Preparation FDG 18 F - NAKED FLUORIDE Cleaning Nuclear Interface H O O O O 18 F H H O H [ 18 F]FDG 18 F De-protection PRECURSOR Nucleophilic substitution INTERMEDIATE

28 [ 18 F]FDG MODULES Nuclear Interface Coincidence Technology FDG microlab (GE) JALTECH (EBCO) IBA CPCU (CTI) Sumitomo Robot (SCX-

29 Clinical PET/CT protocols The biograph Thomas Beyer, PhD

30 Fused Image Tomography Radiology PET/CT scanner Nuclear Medicine Biopsy Surgery IMRT Fused image viewer Pre Post Therapy response Diagnosis and Staging Oncology

31 «Image of the Year» 1999, 46.SNM Los Angeles

32 Dual-modality PET/CT Prototype SMART Tomograph (1998) >300 patients scanned >70 IV contrast exams 110 cm 60 cm 168 cm CT PET T Beyer, DW Townsend, et al., JNM 41 (8): pp 1369, (2000). 100 cm Dual-modality imaging range

33 biograph 158 cm Width 228 cm 90 cm 188 cm CT PET 145 cm Dual-modality imaging range

34 CT - PET or PET CT? CT PET fused anatomy function image CT PET fused anatomy function image The future of cancer diagnostics today state of the art

35 Multi-modality installation

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