Anti–Prostate-Specific Membrane Antigen Liposomes Loaded with225Ac for Potential Targeted Antivascular α-Particle Therapy of Cancer

• DOI: 10.2967/jnumed.113.125476
• Publication Date: 2013-12-13T03:36:30Z
• Authors: Amey Bandekar; Charles Zhu; Rohit Jindal; Frank Bruchertseifer; Alfred Morgenstern; Stavroula Sofou
• Keywords: Glutamate carboxypeptidase II; Aptamer; Internalization

This study evaluates targeted liposomes loaded with the α-particle generator ²²⁵Ac to selectively kill prostate-specific membrane antigen (PSMA)–expressing cells aim assess their potential for antivascular radiotherapy. <b>Methods:</b> In this study, PEGylated were and labeled mouse antihuman PSMA J591 antibody or A10 aptamer. The targeting selectivity, extent of internalization, killing efficacy evaluated on monolayers prostate cancer intrinsically expressing (human LNCaP rat Mat-Lu cells) HUVEC induced express (induced HUVEC). <b>Results:</b> loading efficiency into preformed ranged from 58.0% ± 4.6% 85.6% 11.7% introduced radioactivity. conjugation reactions resulted in approximately 17 2 antibodies 9 aptamers per liposome. average size liposomes, 107 nm diameter, was not affected by loading. exhibit 2:1:0.5 relative expression, compared MatLu HUVEC, respectively, based flow cytometry detecting association antibody. J591-labeled display higher levels total specific binding all cell lines than aptamer-labeled liposomes. Specific increases incubation time. Cytotoxicity studies demonstrate that radiolabeled are most cytotoxic, median lethal dose values, after 24 h incubation, equal 1.96 (5.3 × 10⁻⁵), 2.92 10² (7.9 10⁻³), 2.33 10¹ Bq/mL (6.3 10⁻⁴ μCi/mL) LNCaP, Mat-Lu, which comparable values For aptamer–labeled corresponding 3.70 (1.0 1.85 10³ (5.0 10⁻²), 4.07 (1.1 10⁻¹ μCi/mL), respectively. <b>Conclusion:</b> Our anti-PSMA–targeted bind, become internalized, PSMA-expressing including endothelial PSMA. These findings—combined unique ability be easily tuned, terms surface modification, optimizing biodistributions—suggest PSMA-targeting encapsulating emitters selective α