Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies.
Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies.
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DOI：
10.1016/j.nucmedbio.2012.01.010
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发表时间：
2012-10
影响因子：
3.1
通讯作者：
Muzik O
中科院分区：
文献类型：
--
作者：
Juhász C;Nahleh Z;Zitron I;Chugani DC;Janabi MZ;Bandyopadhyay S;Ali-Fehmi R;Mangner TJ;Chakraborty PK;Mittal S;Muzik O
通过犬尿氨酸途径的色氨酸氧化是肿瘤免疫耐受的重要机制。通过血清素途径增加色氨酸代谢与乳腺癌的恶性进展有关。在这项研究中，我们结合定量正电子发射断层扫描（PET）和肿瘤免疫组织化学分析色氨酸转运和代谢在乳腺癌。在9名II-IV期乳腺癌女性中进行了动态α-[11 C]甲基-L-色氨酸（AMT）PET。在所有肿瘤中进行PET示踪剂动力学建模。通过切除肿瘤标本的免疫染色评估L型氨基酸转运蛋白1（LAT 1）、吲哚胺2，3-双加氧酶（IDO;犬尿氨酸途径的起始酶和限速酶）和色氨酸羟化酶1（TPH 1; 5-羟色胺途径的起始酶）的表达。7例肿瘤AMT摄取在注射后5-20 min达到峰值;另2例显示长期示踪剂蓄积。肿瘤SUV变化很大（2.6-9.8），并显示出与动力学分析得出的分布容积值的强正相关性（p<0.01）。浸润性导管癌（n=6）显示特别高的AMT SUV（范围：4.7-9.8）。在大多数肿瘤细胞中检测到LAT 1、IDO和TPH 1的中等至强免疫染色。乳腺癌在动态PET上显示出不同的色氨酸动力学。注射后5-20分钟测量的SUV合理地反映了示踪剂的分布体积。进一步的研究是必要的，以确定在这些肿瘤中的体内AMT积累是否与色氨酸代谢通过犬尿氨酸和5-羟色胺途径。
Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Dynamic alpha-[11C]methyl-L-tryptophan (AMT) PET was performed in 9 women with stage II-IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway), and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Tumor AMT uptake peaked at 5–20 min post-injection in 7 tumors; the other 2 cases showed protracted tracer accumulation. Tumor SUVs varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (p<0.01). Invasive ductal carcinomas (n=6) showed particularly high AMT SUVs (range: 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 minutes post-injection reflect reasonably the tracer’s volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.
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影响因子：
9.8
作者：
Kaper T;Looger LL;Takanaga H;Platten M;Steinman L;Frommer WB
通讯作者：
Frommer WB
影响因子：
7.3
作者：
Esseghir, S.;Reis, J. S.;Isacke, C. M.
通讯作者：
Isacke, C. M.
影响因子：
3.1
作者：
Batista, Carlos E. A.;Juhasz, Csaba;Chugani, Diane C.
通讯作者：
Chugani, Diane C.
影响因子：
6.3
作者：
Juhász, C;Chugani, DC;Chugani, HT
通讯作者：
Chugani, HT
影响因子：
4.3
作者：
Jia, Lee;Schweikart, Karen;Munn, David H.
通讯作者：
Munn, David H.