Imaging of Vx‐2 rabbit tumors with ανβ3‐integrin‐targeted 111In nanoparticles

Open Access
Publisher Website
Google Scholar
Abstract
Earlier tumor detection can improve 5‐year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. ανβ3‐Targeted 111In 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. ανβ3‐Targeted 111In/NP bearing ∼10 111In/NP vs. ∼1 111In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand‐targeting specificity. ανβ3‐Integrin‐targeted NP with ∼10 111In/NP provided better (p < 0.05) tumor‐to‐muscle ratio contrast (6.3 ± 0.2) than ∼1 111In/NP (5.1 ± 0.1) or nontargeted particles with ∼10 111In/NP (3.7 ± 0.1) over the initial 2‐hr postinjection. At 18 hr, mean tumor activity in rabbits receiving ανβ3‐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 ανβ3‐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 (t1/2β) was estimated to be ∼5 hr using a 2‐compartment model. ανβ3‐Targeted 111In 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.