Reduction of renal uptake of 111 I n‐ DOTA ‐labeled and A 700‐labeled RAFT ‐ RGD during integrin α v β 3 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 G elofusine 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. G elofusine significantly induced a >50% reduction of the renal reabsorption of 111 I n‐ DOTA ‐ RAFT ‐ RGD and A 700‐ RAFT ‐ RGD , without affecting tumor uptake. Injection of G elofusine 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)