Preclinical Evaluation of ^203/212Pb-Labeled Low-Molecular-Weight Compounds for Targeted Radiopharmaceutical Therapy of Prostate Cancer.

ABSTRACT: Targeted radiopharmaceutical therapy (TRT) using α-particle radiation is a promising approach for treating both large and micrometastatic lesions. We developed prostate-specific membrane antigen (PSMA)-targeted low-molecular-weight agents for ²¹²Pb-based TRT of patients with prostate cancer (PC) by evaluating the matching γ-emitting surrogate, ²⁰³Pb. Methods: Five rationally designed low-molecular-weight ligands (L1-L5) were synthesized using the lysine-urea-glutamate scaffold, and PSMA inhibition constants were determined. Tissue biodistribution and SPECT/CT imaging of ²⁰³Pb-L1-²⁰³Pb-L5 were performed on mice bearing PSMA(+) PC3 PIP and PSMA(-) PC3 flu flank xenografts. The absorbed radiation dose of the corresponding ²¹²Pb-lab

SUBMITTER: Banerjee SR 

PROVIDER: S-EPMC6954458 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature