Département de chimie moléculaire

64Cu-cyclam-RAFT-c(-RGDfK-)4, an $\alpha$V$\beta$3 integrin-targeting tetrameric cyclic RGD peptide probe, is a potential theranostic compd. for positron emission tomog. (PET) of tumor angiogenesis and for internal radiotherapy owing to the multiple decay modes of 64Cu. Since kidneys are dose-limiting organs in internal radiotherapy, we aimed to reduce the renal accumulation of 64Cu-cyclam-RAFT-c(-RGDfK-)4 by co-injection with Gelofusine (GF), a succinylated gelatin soln., and/or L-lysine (Lys), and to explore, for the first time, the related mechanisms using the noninvasive and quant. PET imaging technol. Biodistribution assays, dynamic and static PET scans, and metab. studies with radio-thin-layer chromatog. (radio-TLC) were performed in healthy or $\alpha$V$\beta$3-pos. tumor-bearing mice. In the results, co-injection with GF markedly reduced the renal uptake and slightly increased the tumor uptake of 64Cu-cyclam-RAFT-c(-RGDfK-)4. L-Lysine alone had no effect on the probe biodistribution, but the combined use of Lys and GF tended to enhance the effect of GF. Dynamic PET and metabolite anal. by radio-TLC highly revealed that GF blocks the renal reabsorption of 64Cu-cyclam-RAFT-c(-RGDfK-)4, but does not interfere with its metab. and excretion. In conclusion, administration of GF and Lys is a useful strategy for kidney protection in 64Cu-cyclam-RAFT-c(-RGDfK-)4-based internal radiotherapy. [on SciFinder(R)]