Abstract
1172
Objectives 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RAFTRGD) is a novel tetrameric cyclic RGD peptide probe for PET imaging of tumor angiogenesis via targeting the αVβ3 integrin. Because 64Cu also emits β-, it can be used for internal radiotherapy. We studied the effects of a succinylated gelatin-containing plasma expander Gelofusine and L-lysine on the renal uptake and retention of 64Cu-RAFTRGD in tumor-bearing mice, aiming to find measures to lower the risk of nephrotoxicity in internal radiotherapy using 64Cu-RAFTRGD.
Methods Normal or tumor-bearing mice received injection of 64Cu-RAFTRGD with or without co-injection of Gelofusine, L-lysine, or the both. Biodistribution studies were performed at 3 and 24 h post-injection (p.i.). Dynamic PET scans (5 min/frame) were performed at 0-60 min p.i., followed by static PET scans at 3.5 and 24 h p.i. Radio-TLC was done to analyze the radioactive metabolites in blood, urine, liver, and kidney samples at 1 and 24 h p.i.
Results Co-injection of Gelofusine significantly reduced the renal uptake and retention of 64Cu-RAFTRGD. Although L-lysine alone had no influence on the renal radioactivity accumulation, it showed the tendency to enhance the inhibitory effect of Gelofusine. The uptake of 64Cu-RAFTRGD in the tumors was not influenced by co-injection of Gelofusine or together with L-lysine. Dynamic PET imaging of mice and metabolic analysis of tissue samples clearly showed that Gelofusine did block the renal reabsorption of 64Cu-RAFTRGD, and did not interfere with the metabolism and excretion pathway of the probe.
Conclusions Administration of Gelofusine or together with L-lysine is a promising measure for kidney protection in internal radiotherapy using 64Cu-RAFTRGD.