核醫(yī)學(xué)教學(xué)課件：腫瘤顯像

1、Tumor Imaging PET（PET/CT） Imaging OthersPart IPET（PET/CT） Imaging 葡萄糖和18F-FDG的分子結(jié)構(gòu)比較 18F-FDG: Century MoleculeMechanism of 18F-FDG Uptake in tumor cellsF-18-Flurodeoxyglucos 6-P-FDG Glucose CO2 + H2OCell 6-P-glucoseGluthexokinaseGlucose 6 phosphatase1.Increased expression of glucose transporter mole

2、cules at the tumor cell surface;2.Increased amounts/activity of hexokinase;3.Reduced amounts of glucose 6 Phosphatase versus most normal tissues.FDG Uptake Ratios in Tumors荷人腫瘤模型注射18F-FDG 2h后 瘤/血液比值Fused PET/CT scatter correction attenuation correctionSpiral CT: 1-2 min4080 mAs; 140 kVpWB PET: 28 mi

3、n60 min uptakePETCTPET18F-FDG58 mCi I.V.C TFUSIONRESTMethodsImage AnalysisVisual interpretationQuantitative analysis Standardized uptake value (SUV)（標(biāo)準(zhǔn)攝取比值） tissue concentration (MBq/g) injected dose / body weight Metabolic Rate of Glucose (MRGlu)（葡萄糖代謝率） Tumor/nontumor uptake ratios (T/N) SUV =18F-

4、FDG PET : Normal Image(coronal images)假陽(yáng)性生理性攝?。和僖合偌邦^頸部淋巴組織、甲狀腺、棕色脂肪、胸腺、哺乳乳房、乳暈、骨骼肌和平滑肌、消化道、泌尿系統(tǒng)、女性生殖系統(tǒng)（經(jīng)期子宮及卵巢黃體囊腫）炎癥：術(shù)后炎癥、感染或出血，活檢部位，截肢部位；放療后；化療后；局部的炎性病變（結(jié)節(jié)病、真菌感染、分枝桿菌感染）；造瘺部位（氣管、結(jié)腸等）；注射部位；甲狀腺炎；食管炎、胃炎、炎性腸?。患毙曰蚺及l(fā)的慢性胰腺炎；急性膽管炎和膽囊炎；骨髓炎、近期的骨折、關(guān)節(jié)假體；淋巴結(jié)炎良性腫瘤：垂體腺瘤、腎上腺腺瘤、甲狀腺濾泡狀腺瘤、唾液腺腫瘤（Warthins 腫瘤 或 多形性腺瘤）、

5、結(jié)腸腺瘤樣息肉和絨毛狀腺瘤、卵巢的卵泡膜細(xì)胞瘤和囊腺瘤、巨細(xì)胞瘤、動(dòng)脈瘤樣骨囊腫、平滑肌瘤增生和發(fā)育不良：Graves 病，Cushings 病，骨髓增生（貧血或細(xì)胞因子治療），胸腺增生（化療后），骨纖維異常增生癥，Pagets 病缺血：冬眠心肌偽影：PET、CT未配準(zhǔn)導(dǎo)致衰減校正偽影，金屬和高密度鋇劑的偽影棕色脂肪卵巢及乳腺生理性攝取亞甲炎肌肉偽影腸道偽影技術(shù)偽影：CT與PET融合誤差假陰性病灶?。?0 ng/dLnot breast masses or regional nodesCT/MRI neg for extra-pelvic metsnot regional nodesonly

6、non-small cellwhen enrolled in NOPRCED, coverage with evidence development; NC, non-covered;Clinical IndicationDetect occult lesionsDistinguishing between malignant and benign disease (良惡性病變鑒別)Malignant disease staging and grading (臨床分期和分級(jí)) Treatment planning (制定治療方案)Radiotherapy planning (輔助制定放療計(jì)劃)

7、Differentiating remains/recurrent disease from radiotherapy/ surgery-induced necrosis/ scar(放療/術(shù)后殘留/復(fù)發(fā)與壞死/瘢痕組織鑒別）Monitoring response to therapy and evaluating prognosis（療效監(jiān)測(cè)評(píng)價(jià)，預(yù)后判斷）Searching for primary lesion（尋找原發(fā)腫瘤病灶）Lung cancerTNM staging treatment planning prognosis evaluating superior to CT Mon

8、itoring response to therapy and detecting recurrent diseaseFDG PETCTStudies1429Number of patients5142,226Sensitivity79%60%Specificity91%77%SPN (Solitary pulmonary nodule)Meta-analysisSquamous cell carcinoma（鱗狀細(xì)胞癌）CT: benign lesion in left inferior lobePET/CT: benign lesion Histology: hamartoma（錯(cuò)構(gòu)瘤）A

9、 51-year-old man, recurrent cough and emptysis for 4 monthsChest CT: benign lesion in right lungOther examinations（bronchoscope and sputum examination）:normalPET/CT: intense uptakemalignant lesion Histology: Squamous cell carcinoma 左側(cè)胸水待查，支纖鏡左支氣管充血腫脹、左下葉支氣管狹窄CT未發(fā)現(xiàn)病灶，胸水癌細(xì)胞（），CEA（）PET：左葉肺癌穿刺活檢：低分化腺癌ad

10、enocarcinoma Tuberculoma(結(jié)核球)CT: multi-lesion in right lungPET: intense uptakeHistology： inflammatory granuloma (炎性肉芽腫) Lung cancer with mediastinal lymph nodes metastasisLung cancer with brain metastasisLung cancer with liver，adrenal gland and osseous metastasesLung cancer with mediastinum lymph no

11、des， liver metastases肺癌伴縱膈淋巴結(jié)、雙肺、腎上腺、腦及廣泛骨轉(zhuǎn)移surgeryNo surgerySome surgeryMonitoring Response63 year old man stage 3A lung cancer, has received 4 cycles of chemotherapy 肺癌化療后Breast cancerSensitivity 82%100%Specificity 68%100%Sensitivity 79%100%Specificity 66%100%。 Distinguishing between malignant and

12、 benign breast tumor Detecting axillary lymph nodes metastasis Detecting recurrent disease or remains post-surgery Monitoring response to therapy and evaluating prognosisBreast cancerBreast cancer with axillary lymph node metastasisBreast cancer with lymph nodes and osseous metastases乳腺癌伴淋巴結(jié)、肝、骨轉(zhuǎn)移3

13、years after mammectomy, liver metastasisA 65-year-old female, 5 years after mammectomy of left breast. PET-CT: intense uptake at left supraclavicular and mediastinal lymph node metastasis 監(jiān)測(cè)和評(píng)價(jià)治療反應(yīng)Breast cancer case, chemohormonotherapy Follow-up: 0, 21, 42, 63 days監(jiān)測(cè)和評(píng)價(jià)治療反應(yīng)Breast cancer, after thre

14、e cycles of chemotherapy. A mammectomy required.Tumor of digestive system18F-FDG 評(píng)價(jià)結(jié)直腸癌探測(cè)結(jié)直腸癌肝轉(zhuǎn)移準(zhǔn)確性 PET 92%，常規(guī) CT78%，CT門脈造影80%。肝外轉(zhuǎn)移檢出率 PET 92%，CT 71%。對(duì)378例患者的研究顯示: 27%的患者18F-FDG PET查出原來(lái)未發(fā)現(xiàn)的轉(zhuǎn)移灶 37%的患者治療方案因PET結(jié)果修訂對(duì)于血清CEA升高而常規(guī)影學(xué)檢查結(jié)果陰性的患者，有必要進(jìn)行PET檢查。A 45-year-old female,3 years post colectomyCEA: increa

15、sedPET-CT: intense uptake at ascending colon and mesenteric lymph nodes recurrent cancer with metastasisRectal carcinoma直腸癌伴多發(fā)淋巴結(jié)Mpancreatic cancerPancreatic cancer with liver metastasesLiver cancerPET-CT: increased uptake in left liver and portal veinliver cancer with tumor embolus in portal veinA-

16、C：HCC Grade1(Edmondson and Steiner分級(jí)). A：CT low density；B：18F-FDG no uptake；C：11C-acetate high uptake (pancreas metastasis).D-F：HCC Grade3 (Edmondson and Steiner分級(jí)). D：CT low density；E：18F-FDG high uptake；F：11C-acetate no uptake.Stomach cancerEsophageal cancer with liver metastasis吻合口復(fù)發(fā)伴縱膈淋巴結(jié)轉(zhuǎn)移食管癌術(shù)后

17、肝門與胰頭間淋巴結(jié)MLymphomaDiagnosisClinical StagingMonitoring response to therapy18F-FDG PET/CT已經(jīng)建議作為惡性淋巴瘤的初始分期、再分期及療效隨訪的標(biāo)準(zhǔn)影像技術(shù)。彌漫大B淋巴瘤（FUO）Lymphoma（right tonsil） with cervical lymph node metastasis 女，21歲，學(xué)生。多漿膜腔積液待查顏面浮腫三月，加重伴呼吸困難半月，發(fā)現(xiàn)縱隔淋巴結(jié)腫大一周入院。三次心包積液細(xì)胞學(xué)檢查均見(jiàn)可疑瘤細(xì)胞。 CT：縱隔內(nèi)多發(fā)淋巴結(jié)腫大，心包少量積液。 骨穿：骨髓增生明顯活躍。 細(xì)胞學(xué)：NH

18、L。Non-Hodgkins lymphomaNHL縱隔及腹膜后等廣泛淋巴侵犯Hodgkins lymphoma with spinal marrow involvement淋巴瘤浸潤(rùn)淋巴結(jié)、肝、脾、骨髓 （NK/T），NH LymphomaDeauville 標(biāo)準(zhǔn) Pre-TherapyPost-TherapyHead and Neck CancerDiagnosisDetecting the recurrent or remainsMonitoring response to therapyNasopharyngeal carcinomaNasopharyngeal carcinoma w

19、ith cervical lymph nodes metastasis（鼻咽癌伴頸部淋巴結(jié)轉(zhuǎn)移）A 32-year-old malePre-radiotherapy: right nasopharyngeal carcinoma with both sides lymph nodes metastasis. Post-radiotherapy: right nasopharyngeal carcinoma and right lymph nodes metastasis disappeared but left lymph nodes metastasis remainedpre-radiot

20、herapypost-radiotherapyA 25-year-old man with Nasopharyngeal carcinoma , 2 years post-radiotherapy.PET-CT: intense uptake recurrent carcinomaLaryngocarcinomaBrain cancerArachnoid cyst (蛛網(wǎng)膜囊腫)Glioma (右額神經(jīng)膠質(zhì)瘤)Glioma III-IV 鑒別腫瘤放療后壞死 /復(fù)發(fā) 腦腫瘤放射壞死A: MR T1加權(quán)圖象，病灶邊緣呈增強(qiáng)征象。B：PET 圖象顯示病灶無(wú)FDG攝取 A BRecurrent dis

21、ease 1 month post-surgeryA year post-surgeryThyroid Cancerfollicular adenocarcinoma(甲狀腺濾泡樣腺癌)follicular adenocarcinoma(甲狀腺濾泡樣腺癌)Melanoma with inguinal lymph node metastasis Searching for Unknown Primary TumorsThe criteria for the diagnosis of UPT Biopsy-proven malignancy (For a cancer that could not

22、 have origin at the biopsy site) No primary tumor found after a thorough medical history or physical examination (including breast and pelvic examination in women and testicle and prostate examination in men) Normal laboratory test results, including the results of a complete blood count, blood chem

23、istry, chest X-ray, computed tomography (CT) scan of the abdomen and pelvis, and mammography or prostate-specific antigen (PSA) test Cancer 2004,100:1776-1785. a 58-year-old male with brain metastasis (be surgically removed). A: The whole body PET image showed increased uptake (red arrow). B: Focus

24、tracer uptake was shown in the right apex (red arrow). Histology confirmed to be large-cell anaplastic carcinoma.OthersHealth examination（？）Sampling directionHealthy Examination A 42-year-old femalePET-CT: intense uptake in right thyroidmalignantHistology: papillary adenocarcinoma體檢疑乳腺癌Healthy Exami

25、nationPET-CT: intense uptake at mid-low part of esophagus, SUVave 3.6, SUVmax 7.2; Sampling was taken by gastroscopy according to PET/CTcarcinoma in situ（原位癌）, be confirmed by histology after surgery腫瘤生物調(diào)強(qiáng)與適形放療Multi dimensional conformal radiotherapy, MDCRT （物理適形與生物適形結(jié)合） 根據(jù)腫瘤不同部位的活性使用不同的放療劑量PET/CT在放

26、療全過(guò)程中發(fā)揮著獨(dú)特的作用腫瘤定性臨床分期靶區(qū)勾畫(huà)劑量指導(dǎo)療效評(píng)價(jià)PET與臨床決策大約2040的患者因PET檢查而改變了治療方案國(guó)內(nèi)外均在進(jìn)行相關(guān)研究不同國(guó)家和不同病種可能有不同結(jié)果與醫(yī)療保險(xiǎn)制度相關(guān)至少在肺結(jié)節(jié)、結(jié)（直）腸癌可以大大節(jié)省醫(yī)療支出。PET的成本效益分析臨床分期與治療抉擇Problems and Pitfalls False positive findingsNormal physiologyGranulomas and other infectionsAdenomasTumor histologyLesions smaller than 8 mmDiabetes/Non-fas

27、ting patients False negative findings56 year man with HCV, end stage liver disease, and presumed hepatomaStandard CTPET/CTPhysiologic Uptake: Brown FatInfection68 year old man with solitary lung nodule. Biopsy: aspergillosis (曲霉菌）Tuberculosis of lymph nodesClinical Impact of PET/CT More accurate dia

28、gnosis Avoidance of unnecessary tests, and (potentially) harmful procedures Better treatment or management36.5% change in decision to treat or not treatWhy PET-CT?Part IINon-specific positive imaging67Ga-citrate imaging201Tl/99mTc-MIBI imaging 99mTc-(V)-DMSA imagingApoptosis imaging （ 凋亡顯像）Hypoxic i

29、maging （乏氧顯像）Gallium-67 tumor imagingMultiple mechanismFirst used clinically in 1969 for tumor detection in patients with Hodgkins diseaseTumor staging and Evaluation response to therapy of patients with HD or non-HL become the most common clinical indication for 67Ga tumor scintigraphyTumor staging

30、 (Hodgkins disease)Stage IStage IIStage IIIResponse to therapy Primary fibrosarcoma of left superior femur左股骨上端原發(fā)性纖維肉瘤Lung cancerfollicular adenocarcinoma甲狀腺濾泡樣腺癌papillary adenocarcinoma甲狀腺乳頭狀腺癌HyperparathyroidismMediastinal adenoma99mTc-MIBIBreast cancermammary x-ray a nodule in left breast99mTc-MI

31、BIintense uptake in left breast and left axilla (腋窩）histological diagnosis infiltrating tubularcarcinoma with metastasis of left axilla lymph node（浸潤(rùn)性導(dǎo)管癌）a palpable mass in right breast99mTc-MIBIslightly increased uptakehistological diagnosis fibroadenoma（纖維腺瘤）鼠腫瘤模型99mTc-Annexin V凋亡顯像（A為對(duì)照；B為環(huán)磷酰胺處理后

32、24h行凋亡顯像，箭頭處放射性濃聚灶示腫瘤凋亡） Apoptosis imagingHypoxic imaging艾氏腹水癌昆明小鼠模型99mTc-HL91乏氧顯像Specific positive imagingTc-99m MDP bone scan I-131: papillary-follicular thyroid cancerTc-99m HIDA: hepatocyte origin tumorsI-131 MIBG: neural crest tumor (adrenal medulla tumor imaging)I-131 NP-59: adrenal cortical t

33、umor imagingRII (radioimummunoimaging): Radiolabeled monoclonal antibodies against tumor surface antigens Receptor Imaging: Radiolabeled peptide against tumor receptors Gene imaging: Antisense imaging/Report gene imagingDiscussed in other chaptersHot spot of studyWhole body bone scan131I whole body

34、scan131I-MIBG imaging: adrenal medulla tumor商品名及上市時(shí)間單克隆抗體種類核素適用腫瘤OncoScint1994B72.3抗高分子量腫瘤相關(guān)糖蛋白（TAG-72）鼠源性IgG單抗111In結(jié)（直）腸癌，卵巢癌CEA-SCAN1996CEA抗體IMMU-4 Fab片段99mTc結(jié)（直）腸癌ProstaScint19967E11-C5.3 (CYT356)單抗-GYK-DTA和111In的結(jié)合體111In前列腺癌Verluma1996鼠源性抗40kd糖蛋白IgG2b單抗NR-LU-10的Fab片段99mTcSCLC、NSCLC、乳腺癌、卵巢癌、結(jié)腸癌和前

35、列腺癌。Radioimummunoimaging (RII)89Zr 標(biāo)記的抗體熱點(diǎn) 111In-OncoScint imagingA 77 year-old male who presented with rectal cancer in 1995. CEA-Scan Positive 5 Months Before CT Receptor Imaging顯像劑受體腫瘤用 途123I(131I)-MIBG（間碘芐胍）腎上腺素受體嗜鉻細(xì)胞瘤、神經(jīng)母細(xì)胞瘤和甲狀腺髓樣癌等11C-羥基麻黃素腎上腺素受體心臟功能、充血性心力衰竭診斷，心肌存活性，腎上腺素瘤診斷和鑒別診斷111In(99mTc、68Ga)-octreotide(奧曲肽)生長(zhǎng)抑素(SMS)受體神經(jīng)內(nèi)分泌腫瘤（胃腸、胰、腦神經(jīng)內(nèi)分泌腫瘤，小細(xì)胞型肺癌、嗜鉻細(xì)胞瘤和副神經(jīng)瘤、甲狀腺髓樣癌、類癌等）18F-FES（16 a-18F-17 b-estradiol）雌激素受體乳腺癌，內(nèi)分泌治療和療效監(jiān)測(cè)18F-FDHT 雄激素受體前列腺癌，內(nèi)分泌治療