Pharmacodynamic studies

Radiotherapeutic α particle effects on tumor growth and animal survival were assessed using immunocompetent C57BL/6J mice (♀ and ♂; 6–8 weeks old; Jackson Laboratory). Briefly, each animal received SC injections of 10⁵ B16-F10 cells and 8 d later were randomly sorted into 3 groups of 10 animals (5♀ and 5♂ per group). Mice in each group received an IV injection of 11.1 kBq of [²²⁵Ac]αMSH-PEG-Cy5-C′ dot (Group I), 11.1 kBq of [²²⁵Ac]NH₂-PEG-Cy5-C′ dot (Group II), or the 1% HSA injection vehicle (Group III) through retro-orbital sinus injection under anesthesia. The specific activity of the injected C′ dots is 227,484 ± 57,583 GBq/mol (n = 6) and 55 ± 12 pmol was injected. Tumor dimensions were measured using calipers and the volume calculated using the formula: volume = 1/2(length × width²). Mice were sacrificed when tumor was >2000 mm³ or if they exhibited lethargy. Survival was plotted using the Kaplan–Meier method and tumor samples from representative animals were harvested for histopathology.