@misc{oai:repo.qst.go.jp:00065519,
 author = {Jin, Zhao-Hui and Furukawa, Takako and Kumata, Katsushi and Xie, Lin and Yui, Joji and Wakizaka, Hidekatsu and Fujibayashi, Yasuhisa and Zhang, Ming-Rong and Saga, Tsuneo and 金 朝暉 and 古川 高子 and 熊田 勝志 and 謝 琳 and 由井 譲二 and 脇坂 秀克 and 藤林 康久 and 張 明栄 and 佐賀 恒夫},
 month = {Sep},
 note = {Objective: α5β1 Integrin is a major transmembrane receptor for the extracellular matrix protein fibronectin. It plays important roles in tumor angiogenesis, progression, invasion, and metastasis, relates to the resistance to chemotherapy or ionizing radiation, and correlates with the poor prognosis in several types of cancers. The present study was aimed to develop a fibronectin-mimetic peptide (FMP)-based radioligand and to evaluate its potential for positron emission tomography (PET) imaging of α5β1 integrin expression. Methods: FMP was synthesized based on the reported α5β1-specific peptide sequence (1) and conjugated with the NOTA chelate for labeling with fluorine-18 (18F) using a facile method based on chelation of [18F]aluminum fluoride (2). A negative control probe was also produced by replacement of “G” with “A” in the primary binding motif, Arg-Gly-Asp (RGD) structured in FMP. In vitro cell binding and blocking assays, dynamic PET scans, biodistribution assays, and autoradiography were performed using α5β1-positive B16F10 and α5β1-negative SW48 cell lines and murine tumor models. Results: Both FMP and FMP control could be radiolabeled with a reasonable yield of 20% and with the radiochemical purity of 99%. The radiolabeled peptide was found acceptably stable in murine serum in vitro for at least 1 hr. The relative cell binding ratios of 18F-FMP to α5β1-positive cells obviously increased with increasing of the cell density, while negligible binding was observed with α5β1-negative cells as well as with the negative control probe. The cellular binding of 18F-FMP could be competitively inhibited by unlabeled NOTA-FMP and FMP in a similarly dose-dependent manner. In vivo α5β1-positive B16F10 tumors could be clearly visualized by small animal PET within 2030 min post-injection of 18F-FMP. Dynamic PET showed rapid and predominant clearance of 18F-FMP by urinary excretion, with negligible levels of radioactivity accumulation in normal tissues. Biodistribution studies demonstrated that the tumor uptake of 18F-FMP was significantly higher in α5β1-positive tumors versus α5β1-negative tumors, and as expected the accumulation levels of radioactivity in α5β1-positive tumors was found significantly higher with 18F-FMP versus its negative control. Autoradiography studies of tumor sections further demonstrated the specificity of tissue binding of 18F-FMP. Conclusion: A α5β1-specific fibronectin-mimetic peptide was successfully functionalized as a PET probe for noninvasive visualization and quantitative evaluation of the expression levels of α5β1 integrin in tumors. Our study indicates that 18F-FMP is worth being further optimized by improving its binding activity and pharmacokinetic properties., The World Molecular Imaging Congress 2014},
 title = {Development of 18F-labeled fibronectin-mimetic peptide for positron emission tomography imaging of 51 integrin expression},
 year = {2014}
}