Reduction of renal uptake of 111In-DOTA-labeled and A700-labeled RAFT-RGD during integrin αvβ3 targeting using single photon emission computed tomography and optical imaging

Integrin α(v)β(3) expression is upregulated during tumor growth and invasion in newly formed endothelial cells in tumor neovasculature and in some tumor cells. A tetrameric RGD‐based peptide, regioselectively addressable functionalized template‐(cyclo‐[RGDfK])4 (RAFT‐RGD), specifically targets integrin α(v)β(3) in vitro and in vivo. When labeled with indium‐111, the RAFT‐RGD is partially reabsorbed and trapped in the kidneys, limiting its use for further internal targeted radiotherapy and imaging investigations. We studied the effect of Gelofusine on RAFT‐RGD renal retention in tumor‐bearing mice. Mice were imaged using single photon emission computed tomography and optical imaging 1 and 24 h following tracer injection. Distribution of RAFT‐RGD was further investigated by tissue removal and direct counting of the tracer. Kidney sections were analyzed by confocal microscopy. Gelofusine significantly induced a >50% reduction of the renal reabsorption of (111) In‐DOTA‐RAFT‐RGD and A700‐RAFT‐RGD, without affecting tumor uptake. Injection of Gelofusine significantly reduced the renal retention of labeled RAFT‐RGD, while increasing the tumor over healthy tissue ratio. These results will lead to the development of future therapeutic approaches. (C ancer S ci 2012; 103: 1105–1110)