Imaging tumor endothelial marker 8 using an ^sup 18^F-labeled peptide

• Published in: European journal of nuclear medicine and molecular imaging 2011-10, Vol.38 (10), p.1806
• Main Authors: Quan, Qimeng, Yang, Min, Gao, Haokao, Zhu, Lei, Lin, Xin, Guo, Ning, Zhang, Guixiang, Eden, Henry S, Niu, Gang, Chen, Xiaoyuan
• Format: Article
• Language: English
• Subjects: Biomarkers; Cancer; Peptides; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-011-1871-4

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 ^sup 18^F 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 IC^sub 50^ value of 304 nM. Coupling 4-nitrophenyl 2-^sup 18^F-fluoropropionate with QQM gave almost quantitative yield and a high specific activity (79.2±7.4 TBq/mmol, n=5) of ^sup 18^F-FP-QQM at the end of synthesis. ^sup 18^F-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. ^sup 18^F-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.[PUBLICATION ABSTRACT]