核医学nuclearmedicine-.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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,),Radioactive Decay Processes,1.alpha,+,2.,beta minus,-,3.beta plus,+,4.e,-,captureEC,5.isomeric transition,6.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 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 GeneratorColumn Chromatography,When saline is passed,over column,the,99m,TcO,4,-,is dissolved and less,strongly adsorbed to,alumina.,Cardiac Infarction,201,TlCl Rest,99m,Tc-Sestamibi,Stress Test,Cardiac Ischemia,201,TlCl Rest,99m,Tc-Sestamibi,Stress Test,(MDP),(EDP),(HDP),Normal Canine Bone Scan,99m,Tc-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,99m,Tc-HDP,Principle of PET Imaging,Each annihilation produces two 511 keV photons traveling in opposite directions(180,O,)which are detected by the detectors surrounding the subject,G,L,U,T,PLASMA,TISSUE,FDG,Fluorodeoxyglucose Metabolism,18,FFluorodeoxyglucose(FDG),PET,Control,Alzheimers Disease,Center for Functional Imaging;Life Sciences Division;Lawrence Berkeley National Laboratory;Berkeley,CA.,Brain Metabolism,(,18,FFDG),11,CRaclopride 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:,99,Mo,131,I,133,Xe,137,Cs and,90,Sr,Mo-99,I-131,Differentiated,Thyroid,Carcinoma,5 mCi Na,131,I,Imaging,Treatment Planning,48 h p.i.,Differentiated,Thyroid,Carcinoma,Therapy,105 mCi Na,131,I,27 h p.i.,Differentiated Thyroid Carcinoma,Post Surgical Resection,Therapy,57,Co Flood Source+105 mCi Na,131,I,Differentiated Thyroid Carcinoma,201,TlCl and,99m,Tc-Sestamibi Imaging,4 months after Na,131,I Therapy,Canine Osteosarcoma,Tumor distal radius,Story of QuadraMet,TM,-I,153,Sm 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;,153,Sm-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,153,Sm-EDTMP in Canine Osteosarcoma,Response,#of Dogs (%),Survival(months),Disease Free,7 (18%),11-60,Partial Response,25 (62%),1-16,No Response,8 (20%),0.5-1,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,1997,153,Sm-EDTMP QuadraMet,99m,Tc-MDP,153,Sm-EDTMP,N,N,PO,3,H,2,PO,3,H,2,PO,3,H,2,PO,3,H,2,153,Sm,+,Experimental Nuclear Medicine,Targeting vector(e.g.,mAb,peptide hormone,small molecule,etc.),Radionuclide(e.g.,diagnostic,99m,Tc,111,In,etc.;therapeutic,188,Re,90,Y,177,Lu,etc.),Bifunctional chelating agent(BCA),Linker or spacer,The design of an effective tumor-targeting radio-pharmaceutical involves appropriate selection of:,Radiopharmaceutical Design,Targeting,Vector,Linker,Bifunctional,Chelating Agent,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,Chelator,PNA,Peptide,DOTA-Tyr,3,-Octreotate,*M=,111,In for gamma scintigraphy and single photon emission tomography(SPECT),64,Cu for positron emission tomography(PET),or,177,Lu for targeted radiotherapy(TRT).,N,O,N,H,D,P,h,e,C,y,s,T,y,r,D,T,r,p,L,y,s,T,h,r,C,y,s,T,h,r,N,N,N,C,O,O,H,C,O,O,H,C,O,O,H,S,S,*,M,H,O,O,C,PNA and Peptide Conjugates,MicroSPECT/CT Using,111,In-labeledPNA and Peptide Conjugates(1 h,48 h),Antisense,Nonsense,Ala,TATE,Jia F,et al.,J.Nucl.Med,.2008;49:430-438,Bcl-2 mRNA Expression Levelsin Mec-1 and Ramos Cells,3821,1,(Bcl-2+),(Bcl-2-),MicroSPECT/CT Using,111,In-DOTA-anti-,bcl-2,-PNA-Tyr,3,-octreotate(48 h),Mec-1,Ramos,MicroPET/CT Using,64,Cu-DOTA-anti-,bcl-2,-PNA-Tyr,3,-octreotate,Mec-1,Ramos,1 h 3 h 24 h 48 h,Hypothesis 2,Dogs with naturally occurring B-cell,lymphoma will demonstrate tumor,specific uptake of,111,In-anti-,bcl-2,-PNA-,Tyr,3,-octreotate that correlates,negatively with response to,chemotherapy.,111,In-DOTA-Tyr,3,-Octreotate,Scintigraphy,Nodes,1 h post-injection,4 h post-injection,24 h post-injection,PNA Imaging of Normal Dog,Partial Remission,Initial Scan,Remission Scan,Complete Remission,Initial Scan,Remission Scan,Relapse Scan,Hypothesis 3,Combined radionuclide and antisense therapy may act synergistically or additively with respect to cell proliferation and viability in an in vitro model of B-cell lymphoma.,Western Blot Analysis,Tubulin,bcl-2,1 2 3 4 5,1.Cells without treatment,2.Cells treated with 2,g of DOTA-anti-,bcl-2,-PNA-Tyr,3,-octreotate,for 48 h,3.Cells without treatment,4.Cells treated with 2,g of DOTA-nonsense-PNA-Tyr,3,-octreotate,for 48h,5.Cells treated with 2,g of DOTA-anti-,bcl-2,-PNA-Ala for 48 h,Cell Viability Assay,Day 2 p0.002,Day 3 p0.005,TUNEL Assays,Anti-,bcl-2,+Anti-,FLIP,Anti-,bcl-2,+CH11,Anti-,bcl-2,Anti-,FLIP,+CH11,Anti-,bcl-2,+Anti-,FLIP,Anti-,bcl-2,+CH11,Anti-,bcl-2,Anti-,FLIP,+CH11,SH-SY5Y,IMR-32,Acknowledgments,Dr.Carolyn Anderson,Washington University,Dr.Henry VanBrocklin,Lawrence Berkeley Lab,Dr.Joanna Fowler,Brookhaven National Lab,Dr.Gregory Daniel,University of Tennessee,Dr.Alan Ketring,University of Missouri,Dr.Wynn Volkert,University of Missouri,