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METALS IN MEDICINE

METALS IN MEDICINE. APPLICATIONS OF METALS IN MEDICINE AT ANSTO RADIOPHARMACEUTICAL R & D Andrew Katsifis 19 January 2004. Henri BECQUEREL. George. HEVESY. THE RADIOTRACER. the idea. the tool. the concept. Claude BERNARD.

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METALS IN MEDICINE

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  1. METALS IN MEDICINE APPLICATIONS OF METALS IN MEDICINE AT ANSTO RADIOPHARMACEUTICAL R & D Andrew Katsifis 19 January 2004

  2. Henri BECQUEREL George HEVESY THE RADIOTRACER the idea the tool the concept Claude BERNARD

  3. Molecular Imaging in Nuclear Medicine QC/QA RADIOLABELLING RADIOPHARMACOLOGY PET SPECT Precursor Radionuclide Injection Purification Human Radiopharmaceutical

  4. METALS IN MEDICINE Radiopharmaceuticals R&D • Multidisciplinary group: Chemists, Biologists, Pharmacologists, Physicists. • Synthetic Chemistry- Ligand, Conjugates • Drug Synthesis-Receptor Molecules • Separation and Analytical technologies • In vitro and In vivo evaluation (Animal Models) • Autoradiography, Metabolite Analysis • Radionuclide Source- Cyclotron and Reactor • SPECT-CT Animal Imaging(CT-SPECT, PET) • Clinical Trials • Extensive national and international links

  5. Compact system designed for animal studies Dual-head gamma cameras with CT Pinhole Collimators Gamma Camera METALS IN MEDICINE

  6. METALS IN MEDICINE PURPOSE OBJECTIVES Radiopharmaceuticals R&D are Developing Target-Specific Radiolabeled Pharmaceuticals for Diagnosis and Therapy of Disease

  7. METALS IN MEDICINE

  8. METALS IN MEDICINE

  9. METALS IN MEDICINE RATIONALE FOR RADIOPHARMACEUTICAL DESIGN • Few Metals Target Specific Tissues/Organs • 201Tl mimics K, 67Ga-Fe and 89Sr-Ca • For biological activity most other “metallic” radioisotopes must be chelated to form complexes or linked to specific targeting entities

  10. METALS IN MEDICINE RATIONALE FOR RADIOPHARMACEUTICAL DESIGN • Selection of radioisotope for biological use is primarily determined by the isotope’s decay characteristics • Radiopharmaceutical design is based on the intended use, targeting molecules and the physico-chemical properties of isotope. • Nature of the complex will determine biological activity

  11. METALS IN MEDICINE “METAL” ISOTOPE REQUIREMENTS • Emission(g, b+, b-, a) • Radionuclide purity • Specific activity • Half-life • Chemical/physical properties • Ease of production/cost

  12. METALS IN MEDICINE

  13. METALS IN MEDICINE

  14. METALS IN MEDICINE Tc-99m HMPAO (Ceretec)

  15. METALS IN MEDICINE 99mTc HMPAO (Ceretec)

  16. Ictal HMPAO SPECT Inter - Ictal HMPAO SPECT PET

  17. METALS IN MEDICINE 99mTc-MIBI

  18. METALS IN MEDICINE

  19. METALS IN MEDICINE 99mTc-Trodat-Brain Receptor Imaging

  20. METALS IN MEDICINE 99mTc-TRODAT-1 SPECT intransverse views of healthy volunteer (A)and of patients with stage I (B) and stage II (C) Parkinson’s disease. Asymmetric striatal uptake was observed, with more profound loss contralateral to symptoms or more affected limbs.

  21. METALS IN MEDICINE Known Receptor Ligand Receptor Ligand Isotope Isotope Integrated Design Conjugate Design

  22. METALS IN MEDICINE

  23. METALS IN MEDICINE • Receptor target identical • Receptor affinity identical • Pharmacokinetics different • Unit target uptake different • Biodistribution different • Clearance rate different • Clearance route different • Metabolism different • Stability is different

  24. METALS IN MEDICINE Radiopharmaceuticals R&D Interests

  25. 99mTc-RGD Peptide METALS IN MEDICINE

  26. METALS IN MEDICINE Radiopharmaceuticals R&D Interests • Apoptosis • Angiogenesis (avb3 antagonists, MMP’s) • Growth factors (VEGF, EGF) • Receptor-based Tumour targeting (Breast, Melanoma and Prostate) • Peptides • Cell labelling-proteomics

  27. Radiotherapy METALS IN MEDICINE • External beam • Brachytherapy (Radioactive implants) • Restenosis • Particulates (Sirtex-spheres) • Systemic -Radionuclide Therapy (Zevalin-Lymphoma)

  28. Systemic -Radionuclide Therapy METALS IN MEDICINE • Non-invasive delivery of selective radiation to tumours • Combination of brachytherapy and chemotherapy • Limited toxicity- long term effects compare favourably with those of chemotherapy and external beam therapy. • Promising- Advances in molecular targeting technologies (receptors, peptides, MoAbs) and new isotopes • Synergistic effects (Molecular Inhibitors, Hypoxia, Angiogenesis, Selective Cytotoxicity

  29. Opportunities METALS IN MEDICINE • Improvements in targeting strategies-Selectivity and Spepcificity • Reduced Toxicity- clearance • Drug-Delivery • Radionuclide Availability and Costs • Regulatory • Medical Infrastructure

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