Renal uptake and retention of radiopharmaceuticals are dependent not only on the characteristics of the targeting molecule, but also on the

type of radionuclide and chelating agent check details used. We observed that the renal uptake levels of 111In-DOTA-RAFT-c(-RGDfK-)4 and 64Cu-cyclam-RAFT-c(-RGDfK-)4 were substantially different, with biodistributions at 24 h after injection of ∼40%ID/g and ∼10%ID/g, respectively [6] and [19]. Therefore, in this study, we determined the effect of GF on the renal uptake and retention of 64Cu-cyclam-RAFT-c(-RGDfK-)4 in normal and tumor-bearing mice. In comparison with the published work on the 111In-labeled analog, the present study particularly evaluated (1) the dose–effect relationship

of GF, (2) the combined effect of GF and Lys, (3) the spatiotemporal changes in renal radioactivity caused by GF in the presence or absence of Lys (GF ± Lys), and (4) the influence PI3K Inhibitor Library of GF ± Lys on the metabolism of 64Cu-cyclam-RAFT-c(-RGDfK-)4. Another novelty is that the present study explored the mechanisms underlying the action of GF and Lys using the noninvasive and quantitative PET imaging technology. Cyclam-RAFT-c(-RGDfK-)4 (MW 4119.6) was synthesized as reported previously [5], and radiolabeled with 64Cu in accordance with our previous report [6] with minor modifications. In brief, 0.08 mM cyclam-RAFT-c(-RGDfK-)4 in dimethyl sulfoxide and 1.48 MBq/μL 64CuCl2 in ammonium citrate buffer (100 mM, pH 5.5) were mixed in a ratio of 1:1 (v/v) and incubated at 37 °C for 1 h. The radiolabeling efficiency, as determined by reversed phase (RP) high-performance

liquid chromatography, was >98%, and the specific radioactivity was ∼18.5 MBq/nmol. Gelofusine (Braun Medical, Oss, Netherlands), MycoClean Mycoplasma Removal Kit kindly provided by Dr. Lucie Sancey (University of Lyon 1, France), consists of a 40 g/L solution of succinylated gelatin for intravenous infusion, and was diluted in normal saline (NS) for use in the present study. l-Lysine (Sigma–Aldrich, Buchs, Switzerland) was dissolved in NS and added to the injectate prior to administration. Human glioblastoma U87MG cells naturally expressing αVβ3 were cultured as previously described [6]. Animal procedures were approved by Institutional Animal Care and Use Committee of the National Institute of Radiological Sciences (NIRS; Chiba, Japan). Normal or tumor-bearing mice (female BALB/cAJcl-nu/nu; CLEA Japan, Inc., Tokyo, Japan) at 7–8 weeks of age were examined. The tumors, 7–10 mm in diameter, were developed by subcutaneous (s.c.) injection of 1 × 107 cells into the left shoulder region of the mice. Mice were injected via tail vein (i.v.) with 0.74 MBq 64Cu-cyclam-RAFT-c(-RGDfK-)4 with or without co-injection of GF, Lys, or both (GF + Lys). The biodistribution study consists of the following 3 sequential experiments.