To study the pharmacokinetics, 8-10 week old female mice with NT2.5 tumors were injected with the targeted imaging agent In111-DTPA-anti-PD-L1-BC (0.37 MBq) at antibody concentrations of 1-10 mg/kg. Ex-vivo biodistributions were determined at 1,6,24,72, and 144 hours post injection. Short term, the spleen showed higher uptake at lower doses, blood uptake was almost independent of dosage, and liver slightly higher uptake at low dose.
For therapeutic studies, mice were injected 3 days after anti-PD1 antibody injection with either Ac225-DOTA-anti-PD1-BC (15 kBq, 3 mg/kg), or unconjugated antibody at the same concentration, or saline. The Ac225 group showed a significant increase in median survival (63 days, p > 0.05) compared to the saline group. Maximum tolerated dose studies show that doses up to 37 kBq are well tolerated so future studies could go to higher doses.
Presented By: Jessie Nedrow from Johns Hopkins University, Baltimore, MD
Written By: William Carithers, Lawrence Berkeley National Laboratory
at the 10th International Symposium on Targeted Alpha Therapy (TAT-10) May 31 - June 1, 2017 - Kanazawa, Japan.