1. Evaluation of 177 Lu and 47 Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry.
- Author
-
Vaughn BA, Loveless CS, Cingoranelli SJ, Schlyer D, Lapi SE, and Boros E
- Subjects
- Animals, Dipeptides pharmacokinetics, Heterocyclic Compounds, 1-Ring pharmacokinetics, Humans, Male, Mice, Prostate-Specific Antigen pharmacokinetics, Prostatic Neoplasms mortality, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, Chelating Agents chemistry, Dipeptides therapeutic use, Heterocyclic Compounds, 1-Ring therapeutic use, Lutetium therapeutic use, Prostate-Specific Antigen therapeutic use, Prostatic Neoplasms radiotherapy, Radioisotopes therapeutic use, Radiopharmaceuticals therapeutic use, Scandium therapeutic use
- Abstract
Lu-177-based, targeted radiotherapeutics/endoradiotherapies are an emerging clinical tool for the management of various cancers. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) remains the workhorse for such applications but can limit apparent molar activity or efficient charge modulation, which can impact target binding and, as a consequence, target efficacy. Previously, our lab had developed the small, rare earth selective bifunctional chelator, picaga, as an efficient bifunctional chelator for scandium and lutetium isotopes. Here, we assess the performance of these constructs for therapy in prostate-specific membrane antigen (PSMA)-expressing tumor xenografts. To assess the viability of picaga conjugates in conjunction with long in vivo circulation, a picaga conjugate functionalized with a serum albumin binding moiety,
177 Lu-picaga-Alb53-PSMA, was also synthesized. A directly comparative, low, single 3.7 MBq dose treatment study with Lu-PSMA-617 was conducted. Treatment with177 Lu-picaga-Alb53-PSMA resulted in tumor regression and lengthened median survival (54 days) when compared with the vehicle (16 days),47 Sc-picaga-DUPA-,177 Lu-picaga-DUPA-, and177 Lu-PSMA-617-treated cohorts (21, 23, and 21 days, respectively).- Published
- 2021
- Full Text
- View/download PDF