中山腫瘤醫(yī)院講座

1、PET顯像在腦腫瘤診斷中的應(yīng)用,中山大學(xué)附屬第一醫(yī)院核醫(yī)學(xué)科 張祥松,腦解剖特點(diǎn),腦位于堅(jiān)固的顱骨內(nèi)，難以活檢。影像學(xué)檢查是顱內(nèi)病變定性診斷的主要手段。,女，23歲；右額痛2月，Gd-DTPA MRI診斷為腦膠質(zhì)瘤，術(shù)中病理：炎癥。,,常規(guī)影像學(xué)檢查,解剖顯像 CT：平掃＋增強(qiáng) MRI ：T1WI、T2WI，Gd-DTPA增強(qiáng)功能顯像 Perfusion CT imaging：CBF、rCB

2、V、MTT MRI：DWI、DTI、MRS Perfusion MR Imaging (DSC、DCE),A: FLAIR; B:Ga-DTPA; C:DWI; D:ADC; E: rCBV; F&G: MRS,常規(guī)＋功能MRI,,,,,,,,,,Sensitivity > 97%, Specificity ≈ 67%,PET顯像原理,,基本原理：放射性示蹤技術(shù),PET/CT顯像特點(diǎn),功能與解剖成

3、像的完美結(jié)合主要正電子放射性核素均為人體基本組成元素或性質(zhì)相近，其標(biāo)記化合物性質(zhì)基本不變正電子核素分子探針多樣性,PET在腦腫瘤的臨床應(yīng)用,診斷和鑒別診斷腫瘤累及范圍分級(jí)療效預(yù)測(cè)和評(píng)估預(yù)后評(píng)估,腦腫瘤生物學(xué)特性,InvasionIncreased proliferation rateCapability of forming new blood vesselsDecrease rates of cell deathO

4、ver- and underexpression of receptors/tumor antigensHypoxiaNecrosisIncreased metabolism of glucose, amino acids, and membrane precursorsAccelerated rates of apoptosis,PET分子成像靶點(diǎn)：細(xì)胞膜+細(xì)胞內(nèi)+細(xì)胞間質(zhì),葡萄糖代謝－18F-FDG,優(yōu)點(diǎn) 應(yīng)用廣泛，廣譜腫

5、瘤顯像劑，全身顯像 惡性程度分級(jí) 腫瘤復(fù)發(fā)/殘余與放射損傷的鑒別診斷 腦淋巴瘤診斷有價(jià)值 不足 低度惡性腦腫瘤靈敏度低 T/N比值低 假陽(yáng)性,葡萄糖代謝－FDG,右顳葉混合型神經(jīng)膠質(zhì)瘤（Ⅲ級(jí)）。FDG-PET延遲顯像病灶濃聚增加,葡萄糖代謝－FDG,左側(cè)額葉星形細(xì)胞瘤（WHOⅡ級(jí)）,,,,,肺癌腦轉(zhuǎn)移,FDG,13N- NH3,葡萄糖代謝－FDG,葡萄糖代謝－FDG,室管膜瘤術(shù)后殘留或復(fù)發(fā)？隨訪7年未見(jiàn)腫瘤復(fù)發(fā)。,葡萄糖代

6、謝－FDG,間變型少突膠質(zhì)細(xì)胞瘤（Ⅲ級(jí)）術(shù)后復(fù)發(fā),葡萄糖代謝－FDG,Resonfeld et al. J Nucl Med. 1992; 33:532-536,淋巴瘤,化療前 化療后,葡萄糖代謝－FDG,Resonfeld et al. J Nucl Med. 1992; 33:532-536,腦膿腫,,真菌性肉芽腫,FDG假陽(yáng)性,單純皰疹病毒性腦炎,氨基酸類,優(yōu)點(diǎn)靈敏度高T/N比值高顯示腫瘤浸潤(rùn)范圍

7、較準(zhǔn)確不足惡性程度分級(jí)假陽(yáng)性,氨基酸類－MET,18F-FDG PET,11C-MET PET,,,左胼胝體膠質(zhì)瘤（II級(jí)）,氨基酸類－MET,Goldman et al. J Nucl Med 1997; 38:1459-1462,氨基酸類－MET,Tumor Infiltration,Solid Tumor,Kracht et al. Clinical Cancer Research 2004; 10:7163-7170,氨基

8、酸類－FDOPA,Chen et al. J Nucl Med. 2006; 47:908-911,氨基酸類－FET,Edema and Astrogliosis,AstrocytomaGrade Ⅲ,Pauleut et al. Brain 2005;125:678-687,核酸代謝－FLT,Chen. J Nucl Med. 2005; 46:948-952,CONCLUSION: FLT was more sensitive

9、than FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, FLT appears to be a promising tracer as a surrogate marker of

10、 proliferation in high-grade gliomas.,核酸代謝－FLT,R=0.84,R=0.51,Chen. J Nucl Med. 2005; 46:948-952,磷脂代謝－CHO,腦轉(zhuǎn)移瘤檢出率較高,11C-Choline PET 18F-FDG PET,左側(cè)額葉腦轉(zhuǎn)移瘤,18F-FDG,11C-CHOLINE,,,磷脂代謝－CHO,乏氧顯像－FMIS

11、O,Bruehlmeier et al. J Nucl Med. 2004; 45:1851-1859,CONCLUSION: FMISO provide a spatial description of hypoxia in brain tumors that is independent of BBB disruption and perfusion.,乏氧顯像－FMISO,HV: 129cm3, T/B: 3.0T0: 20cm

12、3, T1Gd: 80cm3, T2: 169cm3,HV: 5.3cm3, T/B: 1.6T0: 1cm3, T1Gd: 7cm3, T2: 37cm3,Alexander et al. Clin Cancer Res. 2008; 14: 2623-2630,乏氧顯像－FMISO,Alexander et al. Clin Cancer Res. 2008; 14: 2623-2630,乏氧容積,乏氧比值,腫瘤血管生成－RGD,

13、“In contrast to the relatively disappointing results with other targeted molecular therapies, there has been real progress with agents that inhibit angiogenesis.”,“New developments in targeted molecular therapies for gl

14、ioblastoma” Wen et al. Expert Rev. Anticancer Ther. 2009; 9:7-10,腦腫瘤血管生成,Miller et al. J Natl Cancer Inst. 2005; 95：172-187,腫瘤血管生成－RGD,膠質(zhì)瘤整合素αvβ3表達(dá)增高,Chen et al. J Nucl Med. 2008; 45:1176-118

15、3,氨代謝－NH3,13N-NH3的特性13NH3和13NH4+兩種水化形式存在 13NH4+是K＋的類似物 13NH3脂溶性有限，比乙醇低4-100倍 腦腫瘤組織選擇性表達(dá)GS酶 腦腫瘤組織過(guò)渡表達(dá)K+(ATP)）和（K+(Ca)）,氨代謝－NH3,小分子－－高靈敏度與腦腫瘤特異性結(jié)合－－高特異性,,,13N-NH3,分子量： 547

16、 17,氨代謝－NH3,J Neuro-oncol. 2006; 78:141-151,,氨代謝－NH3,J Neuro-oncol. 2007; 82:305-311,,氨代謝－NH3,,,,PET診斷： 小腦星形細(xì)胞瘤（Ⅳ級(jí)）,,,18F-FDG,13N-NH3,18F-FDG 13N-NH3 11C-MET 11C-CHO,-----腦腫瘤代謝顯

17、像劑,,,,,,,,,MRI增強(qiáng),FDG,NH3,MET,-----低級(jí)別星形細(xì)胞瘤典型代謝表型,星形細(xì)胞瘤II級(jí),星形細(xì)胞瘤II級(jí),,,,,,,,CT/MRI,18F-FDG,13N-NH3,11C-MET,腦膿腫,星形細(xì)胞瘤III級(jí),-----顱內(nèi)感染、炎癥性病變代謝表型,,,,,MRI診斷海綿狀血管瘤合并出血，不除外星形細(xì)胞瘤,PET診斷低級(jí)別星形細(xì)胞瘤,手術(shù)病理：星形細(xì)胞瘤II級(jí),FDG,13N-NH3,11C-MET,,,,

18、MRI,CT,FDG,13N-NH3,,MRI疑診惡性腦腫瘤,PET/CT診斷出血性腦梗死,氨代謝－NH3,,,,ＭＲＩ診斷：右側(cè)顳葉及海馬病變，結(jié)合MRI及DWI表現(xiàn)及既往影像資料，不支持腫瘤，考慮炎性病變可能性大,麥潤(rùn)金 女 55歲，81512,氨代謝－NH3,,,,ＰＥＴ診斷：星形細(xì)胞瘤（Ⅲ級(jí)）,１８Ｆ－ＦＤＧ,１３Ｎ－ＮＨ３,星形膠質(zhì)瘤II級(jí)手術(shù)并放化療后7個(gè)月,18F-FDG顯示輕度攝取,13N-NH3無(wú)攝取,放射性壞死,

19、MRI診斷膠質(zhì)瘤復(fù)發(fā),膠質(zhì)母細(xì)胞瘤,手術(shù)加放化療后三個(gè)月,11C-MET假陽(yáng)性表現(xiàn)(二次手術(shù)證實(shí)為壞死),------氨基酸類PET顯像劑也有假陽(yáng)性!,,,膠質(zhì)母細(xì)胞瘤術(shù)后2周,,,,MRI增強(qiáng),18F-FDG,13N-NH3,膠質(zhì)母細(xì)胞瘤,淋巴瘤,-----腦腫瘤代謝表型差異性,,,,,,,淋巴瘤,18F-FDG,13N-NH3,MRI,,？,MRI,FDG,13N-NH3,膠質(zhì)母細(xì)胞瘤,,,,,？,MRI,FDG,13N-NH3,淋

20、巴瘤,,,,,-----鞍區(qū)腦腫瘤代謝表型差異性,垂體瘤,腦膜瘤,MRI增強(qiáng),18F-FDG,13N-NH3,,,,,,,中山一院院本部MR診斷：腦膜瘤可能性大黃埔院區(qū)MR診斷：鼻咽癌可能性大,MR增強(qiáng),,18F-FDG,13N-NH3,手術(shù)病理：腦膜瘤I級(jí),,,,MR診斷：腦膜瘤臨床疑問(wèn)：泌乳素升高，溴隱亭治療有效，垂體瘤？海綿狀血管瘤？,MR增強(qiáng),18F-FDG,13N-NH3,良性腦膜瘤I級(jí)？,,,,Clin Nucl Med