N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the α_vβ₃ integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed α_vβ₃ integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs. Endothelial cell binding studies showed that copolymer conjugates of approximately 43, 20 and 10 kD actively bind to the α_vβ₃ integrin. Scintigraphic images showed rapid clearance of indium-111 (¹¹¹In) radiolabeled conjugates from the blood pool and high kidney accumulation within 1 h in tumor bearing mice. Biodistribution data confirms images with high accumulation in kidney (max 210% ID/g for 43 kD conjugate) and lower tumor accumulation (max 1.8% ID/g for 43 kD conjugate). While actively binding to the α_vβ₃ integrin in vitro, HPMA copolymer-RGDfK conjugates with increased negative charge through increased CHX-A″-DTPA chelator content in the side chains causes increased kidney accumulation with a loss of tumor accumulation in vivo.