@misc{oai:repo.qst.go.jp:00070233,
 author = {Jin, Zhao-Hui and Furukawa, Takako and Fukumura, Toshimitsu and Saga, Tsuneo and Fujibayashi, Yasuhisa and et.al and 金 朝暉 and 古川 高子 and 福村 利光 and 佐賀 恒夫 and 藤林 康久},
 month = {Sep},
 note = {The alphaVbeta 3-integrin, a well-known transmembrane adhesion receptor plays important roles 
in tumor growth, angiogenesis and metastasis. In this work we evaluate a novel multivalent positron 
emission tomography (PET) probe, 64Cu-cyclam-RAFT-c(-RGDfK-)
4, for alphaVbeta 3-targeted imaging. Methods: Cyclam-RAFT-c(-RGDfK-)4, the conjugate of a chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam) and RAFT-c(-RGDfK-)4, a tetrameric Arg-Gly-Asp (RGD)-based peptide, was radiolabeled with the positron emitter 64Cu. The resultant 64Cu-cyclam-RAFT-c(-RGDfK-)
4was evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies and PET-imaging. The following cell lines, human embryonic kidney HEK293
(beta 1) [alphaVbeta 3-negative] and HEK293(beta 3) [alphaVbeta 3-overexpressing] and human glioblastoma U87MG [naturally expressing alphaVbeta 3], together with their subcutaneous xenografts in athymic nude mice were used for the present study. The levels of alphaVbeta 3expression on these cell lines and tumor xenografts were analyzed by flow cytometry and SDS-polyacrylamide gel electrophoresis/autoradiography, respectively. Results: Cyclam-RAFT-c(-RGDfK-)4 was radiolabeled with 64Cu at 37degree-C for 1 h with high radiochemical purity (~100%) and biostability. 64Cu-cyclam-RAFT-c(-RGDfK-)4targeted the alphaVbeta 3in vitro and in vivo with high affinity and specificity, and displayed rapid blood clearance, predominantly renal excretion, and low-level uptake in nontumor tissues. Tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4(3 h postinjection) in HEK293(beta 3) (high levels of alphaVbeta 3), U87MG (moderate levels of alphaVbeta 3), and HEK293(beta 1) (undetectable levels of alphaVbeta 3) tumors was 9.35 +/- 1.19, 3.46 +/- 0.45, and 1.18 +/- 0.30%ID/g, respectively [%ID/g is percentage of injected dose per gram], with a strong and positive correlation obtained between the tumor uptake values and tumor alphaVbeta 3expression levels. PET images showed that alphaVbeta 3-positive tumors were clearly visualized with high tumor-to-background contrast, and agreed well with the biodistribution results. Conclusion: 64Cu-cyclam-RAFT-c(-RGDfK-)4-based PET is able to visualize alphaVbeta 3positive tumor with high imaging quality, and exhibits potential for noninvasively quantifying alphaVbeta 3 expression., World  Molecular Imaging Congress 2010},
 title = {PET-Imaging of Tumor alphaVbeta3-Integrin Expression with a Novel Probe 64Cu-cyclam-RAFT-c(-RGDfK-)4},
 year = {2010}
}