Imaging of Vx‐2 rabbit tumors with α ν β 3 ‐integrin‐targeted 111 In nanoparticles

Earlier tumor detection can improve 5‐year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. α ν β 3 ‐Targeted 111 In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx‐2 tumor. α ν β 3 ‐Targeted 111 In/NP bearing ∼10 111 In/NP vs. ∼1 111 In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand‐targeting specificity. α ν β 3 ‐Integrin‐targeted NP with ∼10 111 In/NP provided better ( p < 0.05) tumor‐to‐muscle ratio contrast (6.3 ± 0.2) than ∼1 111 In/NP (5.1 ± 0.1) or nontargeted particles with ∼10 111 In/NP (3.7 ± 0.1) over the initial 2‐hr postinjection. At 18 hr, mean tumor activity in rabbits receiving α ν β 3 ‐integrin‐targeted NP was 4‐fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of α ν β 3 ‐targeted fluorescent‐labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half‐life ( t 1/ 2 β ) was estimated to be ∼5 hr using a 2‐compartment model. α ν β 3 ‐Targeted 111 In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary high‐resolution imaging modalities, such as MRI. © 2007 Wiley‐Liss, Inc.