Efficacy and toxicity of radioimmunotherapy with 90Y-DOTA-peptide-ChL6 for PC3-tumored mice

• Published in: The Prostate 2000-08, Vol.44 (3), p.187-192
• Main Authors: O'Donnell, Robert T., DeNardo, Sally J., DeNardo, Gerald L., Miers, Laird, Lamborn, Kathleen R., Kukis, David L., Meyers, Frederick J.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; chimeric L6; Immunotherapy; Medical sciences; nude mice; PC3; Pharmacology. Drug treatments; prostate cancer; radioimmunotherapy
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/1097-0045(20000801)44:3<187::AID-PROS2>3.0.CO;2-C

BACKGROUND Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients. METHODS Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with 90yttrium‐(90Y)‐DOTA‐peptide‐ChL6 (75–260 μCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts. RESULTS RIT produced durable, dose‐dependent antitumor effects with a 100% response rate using 112 μCi and 150 μCi (the maximum tolerated dose) of 90Y‐DOTA‐peptide‐ChL6. Myelotoxicity was reversible, dose‐limiting, and dose‐related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150‐μCi group survived the 84‐day study period vs. 1/8 (13%) for untreated, tumored control mice. CONCLUSIONS 90Y‐DOTA‐peptide‐ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer. Prostate 44:187–192, 2000. © 2000 Wiley‐Liss, Inc.