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Nuclear Medicine

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  1. Nuclear Medicine Michael R. Lewis, Ph.D. Associate Professor Department of Veterinary Medicine & Surgery Department of Radiology Nuclear Science & Engineering Institute

  2. Generally decay by b- emission because of excess neutrons Not many are useful for diagnostic imaging, but several are useful for radiotherapy Generally decay by b+ emission or electron capture because of excess protons Many are useful for diagnostic imaging (gamma scintigraphy or positron emission tomography) Fisson/Reactor Products Cyclotron Products

  3. Definition of Radiopharmaceutical • Radioactive compound used for diagnosis and/or therapy of diseases • In nuclear medicine, ~95% of radiopharmaceuticals used for diagnosis, while the rest are used for therapy • Radiopharmaceuticals have no pharmacologic effect, since they are used in tracer quantities

  4. Ideal Radiopharmaceutical for Imaging -Factors to Consider • Administering to patients • What is the radiation dose to normal organs? • Radiochemical and radionuclidic purity must be extremely high • Regulatory approval required for human use • Scope and limitations of instrumentation • Gamma scintigraphy vs. single photon emission computed tomography (SPECT) vs. positron emission tomography (PET)

  5. Ideal Physical Characteristics of Imaging Radiopharmaceutical • Decay Mode • gamma (gamma scintigraphy) or positron (PET) • a and b- emitters avoided if at all possible; cause higher absorbed dose to organs and tissues • “Good” Energy emissions of radionuclide • Easily collimated and shielded (lower dose to personnel) • easily detected using NaI crystals (e.g. Tc-99m decays by 140 keV photons which is ideal) • low radiation dose to the patient (no a or b)

  6. Ideal Physical Characteristics of Imaging Radiopharmaceutical • Ideal half-life • long enough to formulate RaPh and accomplish imaging study • short enough to reduce overall radiation dose to the patient • physical half-life of radionuclide should be matched well to biological half-life of RaPh • Readily Available • geographic distance between user and supplier limits availability of short-lived radionuclides/RaPh • Generator-produced radionuclides are desirable

  7. Ideal Biological Characteristics of Radiopharmaceutical • Ideal biological half-life • long enough to complete the procedure • (i.e. localize to target tissue while minimizing background) • short enough to reduce overall radiation dose to the patient • High target:non-target ratio • rapid blood clearance • rapid localization in target tissue • rapid clearance from non-target tissues (liver, kidney, intestines)

  8. Radioactive Decay Processes • 1. alpha ++ • 2. beta minus - • 3. beta plus + • 4. e- capture EC • 5. isomeric transition  • 6. Internal conversion IC

  9. Diagnostic Nuclear Medicine

  10. Anatomic vs. Physiologic Imaging

  11. How does Physiologic Imaging Work? Anatomy vs. Function in a broken leg

  12. Anatomy vs. Physiology

  13. Gamma Camera • device most commonly used to obtain an image in nuclear medicine • sometimes called a scintillation camera or Anger camera • camera obtains an image of the distribution of a RaPh in the body (or organ) by detection of emitted g-rays

  14. Gamma Camera Consists of… • A collimator • sodium iodide crystal (detector) • photomultiplier (PM) tube array • position circuit • summation circuit • pulse height analyzer

  15. Sodium Iodide Detector • Gamma rays which interact in the crystal will deposit energy in the crystal to produce “fast electrons” with high kinetic energy • Mechanisms of interaction are: • Photoelectric effect • Compton scatter • Pair production (not relevant to NM)

  16. Sodium Iodide Detector, cont’d... • As electrons slow down in crystal their KE is converted, in part, into light scintillations • A relatively constant proportion of the light scintillations (produced by each g-ray) will exit the crystal and hit the photocathode of the photomultiplier tube • The crystals used in gamma cameras are typically 40-60 cm in diameter and 1 cm thick

  17. Collimator • The purpose of the collimator is to define a field of view • each very small area of the detector ‘sees’ only a small part of the organ to be imaged • two basic types of collimators: • multi-hole (4000-10000 holes) (used more in modern gamma cameras) • single or pin-hole

  18. Gamma Camera Basics* *JPNM Physics website

  19. GE Whole Body Gamma Camera

  20. SPECT Imaging

  21. Mo-99/Tc-99m GeneratorColumn Chromatography When saline is passed over column, the 99mTcO4- is dissolved and less strongly adsorbed to alumina.

  22. Cardiac Infarction 201TlCl Rest 99mTc-Sestamibi Stress Test

  23. Cardiac Ischemia 201TlCl Rest 99mTc-Sestamibi Stress Test

  24. (MDP) (EDP) (HDP)

  25. Normal Canine Bone Scan • 99mTc-MDP (Methylene Diphosphonate)

  26. Rib Metastasis

  27. Juvenile Osteosarcoma 11-year old boy with a one month history of right knee pain Increase activity in the right tibia Diagnosis: Osteosarcoma

  28. Metastatic Prostate Carcinoma Imaging 99mTc-HDP

  29. Principle of PET Imaging • Each annihilation produces two 511 keV photons traveling in opposite directions (180O) which are detected by the detectors surrounding the subject

  30. Fluorodeoxyglucose Metabolism PLASMA TISSUE G L U T FDG

  31. [18F]Fluorodeoxyglucose (FDG)

  32. PET Brain Metabolism ([18F]FDG) Control Alzheimer’s Disease Center for Functional Imaging; Life Sciences Division; Lawrence Berkeley National Laboratory; Berkeley, CA.

  33. [11C]Raclopride PET Brain Study nCi/cc Normal 1000 800 600 Cocaine Abuser 400 200 0 Courtesy BNL PET Project

  34. Therapeutic Nuclear Medicine

  35. I-131 Mo-99 Fission products useful in nuclear medicine include: 99Mo, 131I, 133Xe, 137Cs and 90Sr

  36. Differentiated Thyroid Carcinoma 5 mCi Na131I Imaging Treatment Planning 48 h p.i.

  37. Differentiated Thyroid Carcinoma Therapy 105 mCi Na131I 27 h p.i.

  38. Differentiated Thyroid Carcinoma Post Surgical Resection Therapy 57Co Flood Source + 105 mCi Na131I

  39. Differentiated Thyroid Carcinoma 201TlCl and 99mTc-Sestamibi Imaging 4 months after Na131I Therapy

  40. Canine Osteosarcoma Tumor distal radius

  41. Story of QuadraMetTM -- I • 153Sm identified as a useful nuclide for radiotherapy by MU researchers • Development began in early 1980’s at MU in collaboration with the Dow Chemical Company [phosphonate ligand complexes;153Sm-EDTMP] • Successful in treatment of primary osteosarcoma in canine patients, with added bonus of 18% cure rate [MU College of Veterinary Medicine]

  42. One of Our First Patients

  43. Bone Scans of Canine Patient Before Treatment: 8/15/85 After Treatment: 3/3/86

  44. Results of Clinical Trial of153Sm-EDTMP in Canine Osteosarcoma

  45. Story of QuadraMet™ -- II • Clinical trials began in late 1980’s, with doses supplied by MURR for Phase I studies • ~80% efficacy, with ~25% obtaining full pain remission • Approved in U.S. for pain palliation of metastatic bone cancer in March, 1997

  46. PO H 3 2 PO H 3 2 N N PO H 3 2 PO H 3 2 + 153Sm 153Sm-EDTMP [QuadraMet] 99mTc-MDP 153Sm-EDTMP

  47. Experimental Nuclear Medicine