title: Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer.
abstract: In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.
authors: Medical Isotopes Research Center, Peking University, 38# Xueyuan Road, 100191, Beijing, China.
authors: Jiyun
authors: J
authors: Shi
authors: Zhaofei
authors: Z
authors: Liu
authors: Bing
authors: B
authors: Jia
authors: Zilin
authors: Z
authors: Yu
authors: Huiyun
authors: H
authors: Zhao
authors: Fan
authors: F
authors: Wang
mesh_terms: D000818:Animals; D019281:Dimerization; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008187:Lutetium / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D011868:Radioisotopes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D039302:Integrin alphaVbeta3; D009943:Organophosphorus Compounds; D010456:Peptides, Cyclic; D011868:Radioisotopes; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D008187:Lutetium