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Medical Imaging Workshop Molecular Imaging

Join our workshop to explore molecular imaging in medical research, from in vivo visualization to clinical applications. Learn about imaging modalities, molecular expression, and the latest developments in therapy planning. Discover the role of molecular biology in diseases and explore the spectrum of imaging modalities available for research and clinical use.

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Medical Imaging Workshop Molecular Imaging

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  1. Medical Imaging WorkshopMolecular Imaging Marcelo Tatit Sapienza INFIERI Summer School Intelligent signal processing for FrontIER Research and Industry 

  2. Molecular Imaging • Overview • Imaging Modalities • Clinical Applications – e.g. breast cancer

  3. Molecular Imaging MOLECULAR BIOLOGY In vivo Imaging visualisation, characterization and quantification of normal / pathological biological processes at the cellular and molecular level

  4. MOLECULAR BIOLOGY Molecular paradigm of diseases  Abnormal cells with pathological phenotypes Molecular expression

  5. Hallmarks of cancer – Cell 2000 Hanahan & Weinberg

  6. Abnormal cells with pathological phenotypes Molecular expression Probes / ligandsmaybedetectedandallow Therapy with labeled compounds Diagnosis Identification of targets for drugs Therapy response Therapy planning

  7. Molecular Imaging BASIC / PRECLINICAL RESEARCH • Study of mechanisms of disease development and progression • Detection and activity of receptors and pathways • Pharmacokinetics / pharmacodynamics of target drugs CLINICAL APPLICATIONS • Understanding pathophysiological mechanisms • Diagnosis / Staging • Response to target drugs /individualized therapies

  8. Translational research

  9. Translationalresearch from BENCH to BEDSIDE topublichealth

  10. Molecular Imaging • Overview • Imaging Modalities • Clinical Applications – e.g. breast cancer

  11. ImagingModalities Differences in • Spatial resolution • Depth of evaluation • Ionizing / non-ionizing radiation • Available molecular markers or probes • Detection threshold Optical systems Nuclear Medicine: PET / SPECT MRI Ultrasonography Computed tomography

  12. Imaging modalities Willmann Nature Reviews 2008

  13. Imaging modalities Optical Imaging: lower cost  high-throughput screening for targets low depth penetration  limited clinical translation Nuclear Medicine: higher cost than optical unlimited depth penetration  clinical translation MRI: high resolution and soft tissue contrast / cost and imaging time US: high spatial and temporal resolution / low cost / limited targets CT: high spatial resolution / no target specific imaging Willmann Nature Reviews 2008

  14. Spectrum ofwavelenghts Eletromagnetic radiation Low energy High energy MRI Optical CT / NM Ultra violet Infra red

  15. Optical Imaging fluorescence and bioluminescence Reporter gene (luciferase) Green fluorescentprotein NearInfraredfluorphores (NIR) Prescher Current Opinion in Chemical Biology 2010

  16. NM Radiopharmaceuticals • radiolabeled molecules designed for in vivo application: • PHARMACEUTICAL= molecular structure determining the fate of the compound within the organism • RADIO= radioactive nuclide responsible for a signal detectable outside of the organism e.g. technetium-99m half life 6 hours gamma-ray photon 140 keV

  17. Scintillationcamara Sorenson and Phelps,27 1987 W.B.Saunders

  18. SPECTSingle Photon Emission Computed Tomography

  19. Positron emitters • Positron: • Same mass as electron • opposite electrical charge • annihilation generates a pair of gamma-ray photons – 180º Nuclideshalflife • F-18 110 min • C-11 20 min • N-13 10 min • O-15 1 2 min • Ga-68 68 min • Rb-82 1.3 min

  20. PET Zanzonico Semin Nucl Med 2004

  21. PET SPECT 140 keV 511 keV SPECT / CT 511 keV PET / CT

  22. PET SPECT PET > SPECT • Spatialresolution (humanstudies) • Temporal resolution • Sensitivity • Cost

  23. Molecular ImagingRequirements • Imaging equipment • Target selection • Development of imaging probe / tracer

  24. Developmentofin vivo probes < 5% of in vitro targets allow development of an in vivo tracer • High TARGET concentration • Affinity and specificity • Absence of biological barriers (i.e. endothelium, blood brain barrier, ...) • Stable labeling of compound

  25. Developmentofin vivo probes < 5% of in vitro targets allow development of an in vivo tracer • High TARGET activity / concentration • Affinity and specificity • Absence of biological barriers (i.e. endothelium, blood brain barrier, ...) • Stable labeling of compound • Low BACKGROUND activity • Non-specific accumulation, • Circulating or interstitial activity • Renal or hepatic elimination

  26. Developmentofin vivo probes < 5% of in vitro targets allow development of an in vivo tracer • High TARGET activity / concentration • Affinity and specificity • Absence of biological barriers (i.e. endothelium, blood brain barrier, ...) • Stable labeling of compound • Low BACKGROUND activity • Non-specific accumulation, • Circulating or interstitial activity • Renal or hepatic elimination • Signalamplification • Celltrapping • Enzymaticconversion • "Reporter" molecules: fluorescence, radiation, magnetic

  27. EXAMPLE: 18FDG fluorodeoxyglucose = glucose analogue • Transport (Glut) • Phosphorylation (hexokinase) • Metabolism

  28. MOST TUMORS: Increased Aerobic glycolysis (Warburg effect ) • Phenotype common to most tumors • Lower production of energy / mol • X • NADPH Production - Synthesis • Hypoxiaandacidosisselectcellsresistanttoapoptosis • Acid pH associatedwithinvasion Vander Heiden Understanding the Warburg Effect Science 2009

  29. Hanahan & Weinberg Cell 2011

  30. Molecular Imaging • Overview • Imaging Modalities • Clinical Applications – e.g. breast cancer

  31. Breastcancer • Brazil • Most incident in women • ~ 50 /100,000 • 57.120 new cases ( 2014 – INCA ) deaths: 13.345 ( 2011 – SIM ) 5 y survival ~ 60 % LOBULAR DUCTAL

  32. Breastcancer Therapy choices considers also : • Clinical conditions, Age , Menopause, Histology of the tumor • Hormone Receptors and HER2 Staging - T 1 < 2 cm T2 2-5 cm T3 > 5 cm T4 thoracic wall / skin - N0, 1axillary I-II mobile, N2axillary fixed or int.thoracic, N3infra (III) / supraclavicular / axillary+int. thoracic - Metastases M0, M1 AJCC Cancer Staging Manual. 7th ed. 2010, PROGNOSIS and CONDUCT

  33. Hormone and Growth Factor Receptors expression variation PREDICTIVE biomarker = susceptibility of the tumor before indicating the therapy

  34. BIOPSY: TU hormone receptor ++  susceptible to treatment with drugs that blocks either the estrogen receptors or hormonal synthesis Biomarker-driven personalized cancer therapy Precision medicine  BUT…

  35. Establishing genetic and molecular profile by biopsy may not be sufficient: Tumor heterogeneity Gerlinger, Intratumor heterogeneity NEJM 2012

  36. 18FES – FLUOROESTRADIOL  target = hormone receptor FDG post-therapy FES FDG PREDICTIVE biomarker in breast cancer ( indicates susceptibility to treatment ) Linden JCO 2006

  37. 18FES – FLUORO ESTRADIOL FDG post-therapy FES FDG Linden JCO 2006

  38. EARLY RESPONSE biomarker = post-therapy prognosis PET- FDG in the metabolic evaluation after lymphoma chemotherapy • Reduce or increase # chemotherapy cycles • Change / add therapy Kasamon JNM 2007

  39. 18F-FES – FLUOROTHYMIDINE  target = DNA synthesis uptake after 1st cycle identifies responders ( p 0.001 ) - ( n= 15 ) EARLY RESPONSE biomarker in breast cancer Crippa F Eur J Nucl Med Mol Imaging 2015

  40. 18F-FES – FLUORO THYMIDINE EARLY RESPONSE biomarker in breast cancer uptake after 1st cycle identifies responders ( p 0.001 ) - ( n= 15 ) Crippa F Eur J Nucl Med Mol Imaging 2015

  41. Conclusion • Molecular imagingis a multidiciplinaryfield in theintersectionof molecular biologyandin vivo imaging • Mainpillarsof MI are : • Use ofimagingmodalitieswithdifferent performances • Developmentofprobes/ligandsdetectablein vivo • MI ispartoftranslationalresearchandmaybeapplied for biomarker-driven personalized therapy ( precision medicine )

  42. Thankyou ! marcelo.sapienza@hc.fm.usp.br

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