核醫(yī)學教學課件：01緒論

1、Nuclear MedicineDefinition是研究核技術(shù)在醫(yī)學中的應(yīng)用及其理論的學科。應(yīng)用放射性核素診斷疾病、治療疾病或進行醫(yī)學研究的學科。是醫(yī)學與核物理學、核電子學、化學、生物學以及計算機技術(shù)等學科相融合的產(chǎn)物。包括影像診斷、功能測定、體外分析、核素治療以及示蹤研究。 Nuclear MedicineExperimental Nucl. Med.Clinical Nucl. Med.TherapyInternal radiotherapyRadionuclide application therapyDiagnosisIn vitroIn vivoFunctional imaging

2、Non-imaging ContentFeaturesIn vitro radioassay: RIA, determine the micro substances，high sensitivity,10-18-9gRadionuclide Imaging: blood infusion, metabolism, function, receptor, gene expression-Slices of Life (H.N.WAGNER)Radiotherapy: non-bleeding surgeryDevelopment stories AchievementsMedical appl

3、icationsRadiopharmaceuticalsInstrumentsSocietyNuclear Medicine in ChinaThe history of nuclear medicine is rich with contributions from gifted scientists across different disciplines in physics, chemistry, engineering, and medicine.啊，倫琴，看來消息是真的，并非謠言，也非詭計；這么說，人人都得提防你！你的照片真令人泄氣，最癡情的情人，看到那骨架也絕不會歡喜！1895

4、Roeentgen (Germany): X-RayAntoine H.Becqurel (France，1852-1908)1896年，在研究鈾鹽時，發(fā)現(xiàn)鈾能使附近黑紙包裹的感光膠片感光，從而發(fā)現(xiàn)了Uranium（鈾）的放射性，第一次認識到放射現(xiàn)象。1898，Curie命名放射性-Becqurel射線。1903年，與Curie夫人共獲Nobel物理學獎。Marie S. Curie (1867-1934) 1898，Paris，波蘭化學家Curie 與丈夫 Pierre共同發(fā)現(xiàn)了鐳（Ra，88號元素）。此后，又發(fā)現(xiàn)了Pu（钚）和Th（釷）天然放射性元素。1903，Curie與 Bequere

5、l共獲Nobel物理學獎。1911，Nobel化學獎。 Albert Einstein，1905，解釋光電效應(yīng)，1921物理學獎 Frederick Soddy，1910同位素假說，1920化學獎Francis William Aston，發(fā)明質(zhì)譜儀，證實同位素，1922化學獎A. H. Compton，康普頓效應(yīng)，1927物理學獎Carl David Anderson，發(fā)現(xiàn)正電子，1936物理學獎（Victor Franz Hess 發(fā)現(xiàn)宇宙射線 ）Enrica Fermi，Chicago，用中子輻照和慢中子核反應(yīng)生產(chǎn)出新的放射性核素，1938物理學獎，1942 建立了世界上第一座核反應(yīng)堆，

6、首先生產(chǎn)出放射性碘Irne Curie & Frederic Joliot1934年，法國放射化學家Curie 和她的丈夫 Joliot,第一次用人工核反應(yīng)生產(chǎn)出放射性核素。1935，Nobel化學獎。a粒子 Al 30P1930，University of California, Berkeley，（Lawrence Berkeley National Laboratory）生產(chǎn)出第一臺回旋加速器，并生產(chǎn)出多種同位素。1939，Nobel物理獎。Ernest O. LawrenceGeorge de Hevesy -The father of experimental nuclear med

7、icine建立同位素示蹤技術(shù)，用于植物的代謝研究和人體的生理學研究，并發(fā)明了中子活化分析技術(shù)。1943，Nobel化學獎。Berson & Yalow1960，Berson和Yalow 將核技術(shù)與免疫學技術(shù)結(jié)合建立了放射免疫分析法（RIA）。首先用于測定血漿胰島素濃度。1977，Yalow獲Nobel 生理或醫(yī)學獎。1959 Solomon Berson and Rosalyn Yalow invented the technique of radioimmunoassay to detect insulin antibodies in human serum.1960 John McAfee

8、 and Henry Wagner imaged the kidneys with radiomercury labeled chlormerodrin.1963 Henry Wagner first used radiolabeled albumin aggregates for imaging lung perfusion in normal persons and patients with pulmonary embolism.1963 George V. Taplin developed albumin aggregates for study of phagocytosis by

9、the reticuloendothelial system.1963 B. Ansell and B.M. Cook used radiolabeled colloids for radiation synovectomy.1964 Paul Harper and Katherine Lathrup developed radiotracers labeled with Tc-99m for the study of brain, thyroid and liver.1968 Henry Wagner and colleagues used xenon-133 ventilation sca

10、ns to diagnose pulmonary embolism.1969 C.L. Edwards reported the accumulation of gallium-67 in cancer. 1971 Gopal Subramanian and John McAfee introduced Tc-99m labeled phosphates for bone imaging.1972 David Kuhl performed the first quantitative measurement of cerebral blood volume in living patients

11、.1973 H. William Strauss introduced the exercise stress-test myocardial scan.1973 Elliot Lebowitz introduced thallium-201 for myocardial perfusion imaging, first proposed by Kawana.1973 David Goldenberg demonstrated that radiolabeled antibodies against a human tumor antigen (CEA) could target and im

12、age human tumors in animals.1976 N. Firusian used strontium-89 to reduce pain from metastatic bone disease.1978 David Goldenberg used radiolabeled antibodies to image tumors in humans.1981 J.P. Mach used radiolabeled monoclonal antibodies for tumor imaging.1982 Steve Larson and Jeff Carrasquillo tre

13、ated cancer patients with malignant melanoma using iodine-131 labeled monoclonal antibodies.1983 William Eckelman and Richard Reba carried out the first successful SPECT imaging of a neuroreceptor in humans.1983 Henry Wagner carried out the first successful PET imaging of a neuroreceptor using himse

14、lf as the experimental subject.1990 Steve Lamberts and Eric Krenning imaged endocrine tumors with somatostatin receptor-binding radiotracers.1990 Alan Fischman used indium-111 labeled chemotactic peptides to detect foci of infection.1996 Legitimacy of brain PET1997 Validation of 123I-beta-CIT in ass

15、essing dopamine transporters in the diagnosis of Parkinsons disease.1998 FDG PET studies were used to assess the response of an initial dose of chemotherapy to predict the response to subsequent high-dose chemotherapy. 2007 RT-Image names SNM most influential in radiology.John H. Lawrence - the pion

16、eer of nuclear medicine1936，第一次用人工放射性核素32P治療白血病病人。1983，Enrico Fermi Award。Joseph Gilbert HamiltonPaper published in 1937 detailed early medical trials using radiosodium, followed by papers detailing the use of the radioactive isotopes of potassium, chlorine, bromine, and iodine. died at the age of 4

17、9 of radiation induced leukemia.drinking a radioactive sodium solution in 1939Dr. Hank Kung received the 2013 Kuhl-Lassen Lecture Award from the SNMMI Brain Imaging Council to honor a scientist who has made significant contributions to the field of functional brain imaging using SPECT and PET. Kungs

18、 lecture was entitled, “Amyloid Plaque Imaging Probes: From Bench to Clinic.” Kung is a professor in the Departments of Radiology and Pharmacology at the University of Pennsylvania.1951, Benedict Cassen developed the first rectilinear scanner. “Cassen Award” 1952, David Kuhl invented a photorecordin

19、g system for radionuclide scanning. -the father of emission tomography1957, Hal O. Angers scintillation camera (Anger camera) , also developed the well counter1959, Beginning of emission-computed tomography 1974, First PET camera built for human studies1976, John Keyes developed the first general pu

20、rpose single photo emission computed tomography (SPECT) camera. 1976, Ronald Jaszczak developed the first dedicated head SPECT camera.1986, Highest-resolution PET scanner in the world 1995, ADAC Laboratories shipped the first SPECT camera to offer coincidence detection capable of FDG/PET imaging.199

21、8, SPECT/CT1998, First PET/CT2011, First PET/MRIPET/MRImicro-PET/SPECT/CTmicro-PET/CTmicro-PETmicro-SPECT/CT1954198519801956年,軍委衛(wèi)生部領(lǐng)導，西安第四軍醫(yī)大學舉辦了生物醫(yī)學同位素應(yīng)用訓練班-我國第一個同位素應(yīng)用學習班，1957年舉辦第二期，標志著我國核醫(yī)學的誕生。1958年,北京第一個同位素臨床應(yīng)用訓練班，10名學員-核醫(yī)學進入臨床應(yīng)用的起點。津、滬、穗舉辦24期。20世紀60年代各省相繼開展臨床應(yīng)用工作，同位素和核探測儀器的研制取得重要成績。70年代，在全國得到了普及

22、。1977年核醫(yī)學成為醫(yī)藥院校本科生必修課，教育部和衛(wèi)生部先后組織編寫了多版規(guī)劃教材。1980年成立了中華醫(yī)學會核醫(yī)學分會及各省市核醫(yī)學分會。1981年創(chuàng)辦了中華核醫(yī)學雜志。 2012年中華核醫(yī)學雜志更名為中華核醫(yī)學與分子影像雜志。目前SPECT (/CT) 約700臺，PET/CT 近200臺-2020年，1500臺PET/CT。同濟醫(yī)院核醫(yī)學科最早開展放射性核素臨床應(yīng)用和研究單位之一，1958年原子醫(yī)學教研室，1985年核醫(yī)學科國家臨床重點?？?、教育部重點培育學科博士學位授權(quán)學科、專業(yè)點（1990年）省級核與輻射醫(yī)療救治基地湖北省核學會常務(wù)理事單位湖北省醫(yī)學會核醫(yī)學副主任委員單位核醫(yī)學住院

23、醫(yī)師培訓基地最高端PET/CT、SPECT/CT、回旋加速器、體外分析檢測系統(tǒng)甲狀腺專科門診開展最早，業(yè)務(wù)量位居全省第一培養(yǎng)博士8名、碩士30名主編、副主編、參編教材及著作數(shù)部承擔國家自然基金5項等，獲湖北省科學技術(shù)二等獎Nuclear Medicine自身的理論、方法和應(yīng)用范圍；診斷、治療；門診以及病房；已發(fā)展成為一門完整的臨床學科。Chance and challenge！Future：Radiopharmaceuticals and Instruments Talents！ Radionuclide Imaging Imaging agentsTargetDetection & Imag

24、e processing( CAMERA,SPECT, PET)Radionuclide Imaging CAMERASPECTPETPET/CTUptake mechanism of tracer in tissues and foci合成代謝 131I，131I-6-IC ，18F-FDG 細胞吞噬 99mTc-SC，99mTc-DX，99mTc-HMPAO-WBC循環(huán)通路 99mTc-DTPA，99mTc-RBC ，99mTc-MAA選擇性濃聚 99mTc-PYP ，99mTc-GH，99mTc-MIBI選擇性排泄 99mTc-EC，99mTc-MAG3，99mTc- HIDA 通透彌散

25、 133Xe，99mTc-HMPAO離子交換和化學吸附 99mTc-MDP 特異性結(jié)合 RII，RRI，antisense imaging合成代謝131I18F-FDG細胞吞噬99mTc-PHY通透彌散99mTc-ECD循環(huán)通路99mTc-RBC99mTc-MAA選擇性濃聚99mTc-MIBI選擇性排泄99mTc-DTPA99mTc-EHIDA離子交換和化學吸附 99mTc-MDP 特異性結(jié)合99mTc-TRADOT-1 I-123 MIBG Static & dynamic imaging Classification of radionuclide imaging (1)Static im

26、aging Static & dynamic imaging Classification of radionuclide imaging (1)Dynamic imaging Static & dynamic imaging Classification of radionuclide imaging (1)多相顯像（multiphase imaging） Early artery perfusion imaging Blood pool imaging, 5minDelayed bone imaging, 3hr regional & wholebody imaging Classific

27、ation of radionuclide imaging (2)Regional imaging Whole body imaging Planar & tomographic imaging Classification of radionuclide imaging (3) Planar & tomographic imaging Classification of radionuclide imaging (3)Tomographic imagingPlanar imaging Planar & tomographic imaging Classification of radionu

28、clide imaging (3)Coronal sectionAntPostRL Early & delay imaging Classification of radionuclide imaging (4)99mTc-MIBI雙時相法甲旁亢顯像10min2h Positive & negative imaging Classification of radionuclide imaging (5)131I-AFP RII（+）Colloid imaging（-） Rest & stress imaging Classification of radionuclide imaging (6

29、)Myocardial PerfusionImagingRestStressRestStressStress methods- exercise- pharmaceuticals Single photon & positron imaging Classification of radionuclide imaging (7)Positron imaging Single photon imaging Characteristics of radionuclide imaging 提供臟器、組織、病變的血流、功能等信息，有助于疾病的早期診斷；可全身顯像；可用于定量；具有較高的特異性；安全、無

30、創(chuàng)，符合生理條件；對組織結(jié)構(gòu)的分辨率不及其他影像學方法；SPECT/CT、PET/CT、PET/MRI-多模式圖像的實時融合，功能/代謝影像與解剖結(jié)構(gòu)影像的完美結(jié)合，提供全面的信息。Structure without function is a corpse; function without structure is a ghost. - Stephen A. WainwrightAnatomyBiologyDensityPerfusionMetablismReceptor functionGene expressionFunctionX-rayCTContrastkineticsAngio

31、graphyGamma GameraEchocardiographySPECTMRIMRI spectroscopyMicro-PETMicro-MRIMolecule-anatomy fusion imagingPETPET-CTOptical imagingMolecule Imaging醫(yī)學影像發(fā)展Molecular Imaging Molecular imaging is defined as “the in vivo characterization and measurement of biological processes at the cellular and molecul

32、ar level through the use of imaging devices”. D.J. Wagenaar Acad.Radiol. 8, 409 (2001) 在活體狀態(tài)下，應(yīng)用影像學對細胞和分子水平的生物過程進行定性和定量研究。CONCEPT OF MOLECULAR IMAGING Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochem

33、ical, biologic, diagnostic, or therapeutic application. JNM 2005; 46(9): 11N-14N.分子影像的主要內(nèi)容核醫(yī)學分子成像：代謝顯像、受體顯像、基因顯像、多肽藥物顯像、單抗放射免疫顯像、凋亡顯像、乏氧顯像等磁共振分子成像光學（熒光、發(fā)光）分子成像超聲分子成像（超聲微泡等）臨床前分子影像研究為分子影像學逐步走向成熟，并真正應(yīng)用到新藥的開發(fā)研究、生物治療的臨床前期研究及疾病的分子診斷有重要作用。The main content of molecular ImagingABCDEFrom bench to bedside: Tr

34、anslational BiologyThe comparison of different imagingImage deviceSignalSpace resolutionDepthSensitivityProbe quantityPET1-2mmNo-limit10-1110-12mol/L ngSPECT1-2mmNo-limit10-1010-11mol/LngBiolumines -cenceVisible light3-5mm1-2cm10-1510-17mol/LmgFluorescence imagingVisible light2-3mm 1cm10-910-12mol/L

35、 ugMRIradiowave 25-100umNo-limit10-310-5mol/LCTX ray50-200umNo-limitNot measurementunusedEchoHigh frequency sound wave50-500umcmNot measurement18F-FDG代謝顯像臨床應(yīng)用Tumor神經(jīng)與精神心肌活性Early diagnosis, staging, recurrence and metastasis, efficacy 神經(jīng)、精神疾病、腦功能研究，不同生理刺激或思維活動狀態(tài)腦皮質(zhì)的代謝，腦行為研究區(qū)別心肌壞死、冬眠心肌，為冠心病血運重建治療提供依據(jù)，

36、是判斷心肌細胞活性的“金標準”乳腺癌18F-FES雌激素受體顯像乳腺癌(廣泛性轉(zhuǎn)移),非常好的預后Human Epidermal Growth Factor Receptor 2 (HER2) and HerceptinTrastuzumab (Herceptin)HER2 overexpressionHerceptinTM (Genentech, Inc.)approve in 1998 for treatment ofHER2 positive metastatic breastcancer.HER2 Testing in Current Clinical PracticeImmunohi

37、stochemistry (IHC)BiopsyMicroscopeFluorescent In Situ Hybridization (FISH) Tumor Tissue Molecular Imaging of HER2Potential advantages:1. Non-invasively imaging and monitoring the total expression of the biomarker2. Real time monitoring HER2 status 3. PET has strong quantification ability 4. Low fals

38、e-negative and false-positivePET/CTImagesMRIOISPECT/CTTumor AngiogenesisIntegrin 3 Processes requires integration of the cell into extracellular environment: Cell migration, Angiogenesis, Cell invasion, Tumor growthRole in tumor growth Proliferating vascular endothelial cells Highly angiogenic tumor

39、 cellsIntegrin 3 is a dominant receptor on many types of tumor cells and on activated vascular endothelial cellsRGD peptide(精氨酸、甘氨酸、天門冬氨酸)recognize integrin receptorAnnexin V320 amino acids 36 kDa22 lysine Annexin V is a naturally occurring human protein that binds avidly to membrane-associated phosphatidylserine (磷脂酰絲氨酸,PS). PS is normally found only on the inner leaflet of the cell membrane double layer, but it is actively transported to the outer layer as an early event in apoptosis