核医学nuclearmedicine

Nuclear Medicine,Michael R. Lewis, Ph.D.Associate ProfessorDepartment of Veterinary Medicine & SurgeryDepartment of RadiologyNuclear Science & Engineering Institute,Fisson/Reactor Products Cyclotron Products,Generally decay by b- emission because of excess neutronsNot many are useful for diagnostic imaging, but several are useful for radiotherapy,Generally decay by b+ emission or electron capture because of excess protonsMany are useful for diagnostic imaging(gamma scintigraphy or positron emission tomography),Definition of Radiopharmaceutical,Radioactive compound used for diagnosis and/or therapy of diseasesIn nuclear medicine, 95% of radiopharmaceuticals used for diagnosis, while the rest are used for therapyRadiopharmaceuticals have no pharmacologic effect, since they are used in tracer quantities,Ideal Radiopharmaceutical for Imaging -Factors to Consider,Administering to patientsWhat is the radiation dose to normal organs?Radiochemical and radionuclidic purity must be extremely highRegulatory approval required for human useScope and limitations of instrumentationGamma scintigraphy vs. single photon emission computed tomography (SPECT) vs. positron emission tomography (PET),Ideal Physical Characteristics of Imaging Radiopharmaceutical,Decay Modegamma (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 radionuclideEasily 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-lifelong enough to formulate RaPh and accomplish imaging studyshort enough to reduce overall radiation dose to the patientphysical half-life of radionuclide should be matched well to biological half-life of RaPhReadily Availablegeographic distance between user and supplier limits availability of short-lived radionuclides/RaPhGenerator-produced radionuclides are desirable,Ideal Biological Characteristics of Radiopharmaceutical,Ideal biological half-lifelong enough to complete the procedure(i.e. localize to target tissue while minimizing background)short enough to reduce overall radiation dose to the patientHigh target:non-target ratiorapid blood clearancerapid localization in target tissuerapid clearance from non-target tissues (liver, kidney, intestines),Radioactive Decay Processes,1.alpha+2.beta minus-3.beta plus+ 4.e- captureEC5.isomeric transition6.Internal conversionIC,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 medicinesometimes called a scintillation camera or Anger cameracamera 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 collimatorsodium iodide crystal (detector)photomultiplier (PM) tube arrayposition circuitsummation circuitpulse 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 energyMechanisms of interaction are:Photoelectric effectCompton scatterPair production (not relevant to NM),Sodium Iodide Detector, contd.,As electrons slow down in crystal their KE is converted, in part, into light scintillationsA relatively constant proportion of the light scintillations (produced by each g-ray) will exit the crystal and hit the photocathode of the photomultiplier tubeThe 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 vieweach very small area of the detector sees only a small part of the organ to be imagedtwo 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 GeneratorColumn Chromatography,When saline is passedover column, the 99mTcO4-is dissolved and lessstrongly adsorbed to alumina.,Cardiac Infarction201TlCl Rest99mTc-SestamibiStress Test,Cardiac Ischemia201TlCl Rest99mTc-SestamibiStress 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 kneepainIncrease activity in the righttibiaDiagnosis: Osteosarcoma,Juvenile Osteosarcoma,Metastatic Prostate CarcinomaImaging99mTc-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,GLUT,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,DifferentiatedThyroidCarcinoma5 mCi Na131IImagingTreatment Planning48 h p.i.,DifferentiatedThyroidCarcinomaTherapy105 mCi Na131I27 h p.i.,Differentiated Thyroid CarcinomaPost Surgical ResectionTherapy57Co Flood Source + 105 mCi Na131I,Differentiated Thyroid Carcinoma201TlCl and 99mTc-Sestamibi Imaging4 months after Na131I Therapy,Canine Osteosarcoma,Tumor distal radius,Story of QuadraMetTM - I,153Sm identified as a useful nuclide for radiotherapy by MU researchersDevelopment began in early 1980s at MU in collaboration with the Dow Chemical Company phosphonate ligand complexes;153Sm-EDTMPSuccessful 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 of153Sm-EDTMP in Canine Osteosarcoma,Story of QuadraMet - II,Clinical trials began in late 1980s, with doses supplied by MURR for Phase I studies80% efficacy, with 25% obtaining full pain remissionApproved 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-internalizingReceptors,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-labeledPNA and Peptide Conjugates(1 h, 48 h),Jia F, et al. J. Nucl. Med. 2008; 49: 430-438,Bcl-2 mRNA Expression Levelsin Mec-1 and Ramos Cells,(Bcl-2 +),(Bcl-2 -),MicroSPECT/CT Using111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate(48 h),MicroPET/CT Using64Cu-DOTA-anti-bcl-2-PNA-Tyr3-octreotate,Hypothesis 2,Dogs with naturally occurring B-celllymphoma will demonstrate tumorspecific uptake of 111In-anti-bcl-2-PNA-Tyr3-octreotate that correlatesnegatively with response tochemotherapy.,111In-DOTA-Tyr3-OctreotateSci