Imaging tumor endothelial marker 8 using an 18F-labeled peptide.
Imaging tumor endothelial marker 8 using an 18F-labeled peptide.
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DOI：
10.1007/s00259-011-1871-4
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发表时间：
2011-10
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Quan, Qimeng;Yang, Min;Gao, Haokao;Zhu, Lei;Lin, Xin;Guo, Ning;Zhang, Guixiang;Eden, Henry S.;Niu, Gang;Chen, Xiaoyuan
据报道，肿瘤内皮标记物8（TEM8）在多种癌症类型的肿瘤细胞和肿瘤相关内皮细胞中均上调。TEM8拮抗剂以及靶向TEM8的毒素递送已被开发为有效的癌症治疗方法。对TEM8表达进行成像的能力将有助于评估靶向TEM8的癌症治疗。
从炭疽毒素保护性抗原第IV结构域的小环中鉴定出的一种13肽，KYNDRLPLYISNP（QQM），针对其与TEM8的结合进行了评估，并使用18F标记，用于在UM - SCC1头颈癌和MDA - MB - 435黑色素瘤模型中进行小动物正电子发射断层成像（PET）。
一种改良的酶联免疫吸附测定（ELISA）显示，QQM肽特异性结合TEM8的细胞外血管性血友病因子A（vWA）结构域，半数抑制浓度（IC50）值为304 nM。将4 - 硝基苯基2 - 18F - 氟丙酸酯与QQM偶联，在合成结束时得到近乎定量的产率和高比活度（79.2±7.4 TBq/mmol，n = 5）的18F - FP - QQM。18F - FP - QQM主要经肾脏清除，在高表达TEM8的UM - SCC1肿瘤中的积聚（注射后1小时为2.96±0.84 %ID/g）显著高于低表达TEM8的MDA - MB - 435肿瘤（注射后1小时为1.38±0.56 %ID/g）。
QQM肽特异性结合TEM8的细胞外结构域。18F - FP - QQM肽示踪剂将是一种有前景的用于测量TEM8表达的先导化合物。有必要进一步努力提高示踪剂的亲和力和特异性，并增加其代谢稳定性。
Tumor endothelial marker 8 (TEM8) has been reported to be upregulated in both tumor cells and tumor-associated endothelial cells in several cancer types. TEM8 antagonists and TEM8-targeted delivery of toxins have been developed as effective cancer therapeutics. The ability to image TEM8 expression would be of use in evaluating TEM8-targeted cancer therapy. A 13-meric peptide, KYNDRLPLYISNP (QQM), identified from the small loop in domain IV of protective antigen of anthrax toxin was evaluated for TEM8 binding and labeled with 18F for small-animal PET imaging in both UM-SCC1 head-and-neck cancer and MDA-MB-435 melanoma models. A modified ELISA showed that QQM peptide bound specifically to the extracellular vWA domain of TEM8 with an IC50 value of 304 nM. Coupling 4-nitrophenyl 2-18F-fluoropropionate with QQM gave almost quantitative yield and a high specific activity (79.2±7.4 TBq/mmol, n=5) of 18F-FP-QQM at the end of synthesis. 18F-FP-QQM showed predominantly renal clearance and had significantly higher accumulation in TEM8 high-expressing UM-SCC1 tumors (2.96±0.84 %ID/g at 1 h after injection) than TEM8 low-expressing MDA-MB-435 tumors (1.38±0.56 %ID/g at 1 h after injection). QQM peptide bound specifically to the extracellular domain of TEM8. 18F-FP-QQM peptide tracer would be a promising lead compound for measuring TEM8 expression. Further efforts to improve the affinity and specificity of the tracer and to increase its metabolic stability are warranted.
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DOI：
10.1158/1078-0432.ccr-10-0968
发表时间：
2010-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sun X;Niu G;Yan Y;Yang M;Chen K;Ma Y;Chan N;Shen B;Chen X
通讯作者：
Chen X
影响因子：
4.8
作者：
Rosovitz, MJ;Schuck, P;Leppla, SH
通讯作者：
Leppla, SH
影响因子：
5.7
作者：
Bagley, Rebecca G.;Rouleau, Cecile;Teicher, Beverly A.
通讯作者：
Teicher, Beverly A.
影响因子：
6.4
作者：
Scobie, HM;Thomas, D;Manchester, M
通讯作者：
Manchester, M
影响因子：
11.2
作者：
Cullen M;Seaman S;Chaudhary A;Yang MY;Hilton MB;Logsdon D;Haines DC;Tessarollo L;St Croix B
通讯作者：
St Croix B