Targeting angiogenesis for radioimmunotherapy with a 177 Lu-labeled antibody

摘要: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth tumors, both primary metastatic. CD105, or endoglin, has role number cancers, making widely applicable target for targeted radioimmunotherapy. The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated DTPA radiolabeling 177Lu (t 1/2 6.65 days). Balb/c mice were implanted 4T1 mammary carcinoma cells, five study groups used: only, 177Lu-DTPA-IgG (a nonspecific antibody), 177Lu-DTPA-TRC105 low-dose, high-dose. Toxicity agent monitored by body weight measurements analysis markers. Biodistribution studies also performed at 1 7 days after injection. Ex vivo histology various tissues conducted 1, 7, 30 days injection high-dose 177Lu-DTPA-TRC105. indicated steady uptake tumors between (14.3 ± 2.3%ID/g 11.6 ± 6.1%ID/g, respectively; n = 3) gradual clearance from other organs. Significant inhibition tumor observed group, corresponding significant increase survival (p < 0.001, all groups). In most (all except IgG group), weights did not decrease more than 10%, indicating safety injected agents. Serum alanine transaminase levels remained nearly constant no damage to liver organ agent), confirmed ex histological analyses. 177Lu-DTPA-TRC105, when administered sufficient dose, able provide benefit without off-target toxicity. Thus, could be used combination treatment options allowing effective.