核医学nuclearmedicineppt课件

Nuclear Medicine,Michael R. Lewis, Ph.D. Associate Professor Department of Veterinary Medicine & Surgery Department of Radiology Nuclear Science & Engineering Institute,Fisson/Reactor Products Cyclotron Products,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),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,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),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),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,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),Radioactive Decay Processes,1. alpha + 2. beta minus - 3. beta plus + 4. e- capture EC 5. isomeric transition 6. Internal conversion IC,Diagnostic Nuclear Medicine,Anatomic vs. Physiologic Imaging,How does Physiologic Imaging Work?,Anatomy vs. Function in a broken leg,Anatomy vs. Physiology,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,Gamma Camera Consists of,A collimator sodium iodide crystal (detector) photomultiplier (PM) tube array position circuit summation circuit pulse height analyzer,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),Sodium Iodide Detector, contd.,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,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,Gamma Camera Basics*,*JPNM Physics website,GE Whole Body Gamma Camera,SPECT Imaging,Mo-99/Tc-99m Generator Column Chromatography,When saline is passed over column, the 99mTcO4- is dissolved and less strongly adsorbed to alumina.,Cardiac Infarction 201TlCl Rest 99mTc-Sestamibi Stress Test,Cardiac Ischemia 201TlCl Rest 99mTc-Sestamibi Stress Test,(MDP),(EDP),(HDP),Normal Canine Bone Scan,99mTc-MDP (Methylene Diphosphonate),Rib Metastasis,11-year old boy with a one month history of right knee pain Increase activity in the right tibia Diagnosis: Osteosarcoma,Juvenile Osteosarcoma,Metastatic Prostate Carcinoma Imaging 99mTc-HDP,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,G L U T,PLASMA,TISSUE,FDG,Fluorodeoxyglucose Metabolism,18FFluorodeoxyglucose (FDG),PET,Control,Alzheimers Disease,Center for Functional Imaging; Life Sciences Division; Lawrence Berkeley National Laboratory; Berkeley, CA.,Brain Metabolism (18FFDG),11CRaclopride PET Brain Study,Normal,Cocaine Abuser,Courtesy BNL PET Project,nCi/cc,1000,800,600,400,200,0,Therapeutic Nuclear Medicine,Fission products useful in nuclear medicine include: 99Mo, 131I, 133Xe, 137Cs and 90Sr,Mo-99,I-131,Differentiated Thyroid Carcinoma 5 mCi Na131I Imaging Treatment Planning 48 h p.i.,Differentiated Thyroid Carcinoma Therapy 105 mCi Na131I 27 h p.i.,Differentiated Thyroid Carcinoma Post Surgical Resection Therapy 57Co Flood Source + 105 mCi Na131I,Differentiated Thyroid Carcinoma 201TlCl and 99mTc-Sestamibi Imaging 4 months after Na131I Therapy,Canine Osteosarcoma,Tumor distal radius,Story of QuadraMetTM - I,153Sm identified as a useful nuclide for radiotherapy by MU researchers Development began in early 1980s 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,One of Our First Patients,Bone Scans of Canine Patient,Before Treatment: 8/15/85,After Treatment: 3/3/86,Results of Clinical Trial of 153Sm-EDTMP in Canine Osteosarcoma,Story of QuadraMet - II,Clinical trials began in late 1980s, 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, 1997,153Sm-EDTMP QuadraMet,99mTc-MDP,153Sm-EDTMP,Experimental Nuclear Medicine,Targeting vector (e.g., mAb, peptide hormone, small molecule, etc.) Radionuclide (e.g., diagnostic 99mTc, 111In, etc.; therapeutic 188Re, 90Y, 177Lu, etc.) Bifunctional chelating agent (BCA) Linker or spacer,The design of an effective tumor-targeting radio-pharmaceutical involves appropriate selection of:,Radiopharmaceutical Design,M,Radiometal,Hypothesis 1,Non-invasive imaging of bcl-2 mRNA expression in lymphoma may aid in the identification of chemotherapy patient risk groups, who might respond better to targeted immunotherapy, radioimmunotherapy, or antisense therapy.,Receptor Targeting for Molecular Imaging and Therapy,Radiometal chelation should be stable under physiological conditions. Chelate modification should not lower the receptor binding affinity.,Internalizing vs. Non-internalizing Receptors,Bryan JN, et al. Vet. Comp. Oncol. 2004; 2:82-90,Courtesy of Derek B. Fox, D.V.M., Ph.D.,Peptide Nucleic Acid,Cellular Delivery of PNA,DOTA-Tyr3-Octreotate,*M = 111In for gamma scintigraphy and single photon emission tomography (SPECT), 64Cu for positron emission tomography (PET), or 177Lu for targeted radiotherapy (TRT).,PNA and Peptide Conjugates,MicroSPECT/CT Using 111In-labeled PNA and Peptide Conjugates (1 h, 48 h),Jia F, et al. J. Nucl. Med. 2008; 49: 430-438,Bcl-2 mRNA Expression Levels in Mec-1 and Ramos Cells,(Bcl-2 +),(Bcl-2 -),MicroSPECT/CT Using 111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate (48 h),MicroPET/CT Using 64Cu-DOTA-anti-bcl-2-PNA-Tyr3-octreotate,Hypothesis 2,Dogs with naturally occurring B-cell lymphoma will demonstrate tumor specific uptake of 111In-anti-bcl-2-PNA- Tyr3-octreotate that correlates negatively with response to chemotherapy.,111In-DOTA-Tyr3-Octreotate