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

✍ Scribed by Grace Hu; Michal Lijowski; Huiying Zhang; Kathryn C. Partlow; Shelton D. Caruthers; Garry Kiefer; Gyongyi Gulyas; Phillip Athey; Michael J. Scott; Samuel A. Wickline; Gregory M. Lanza

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 323 KB
• Volume: 120
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22581

✦ Synopsis

Abstract

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.