Alpha- versus Beta-Particle Radiopeptide Therapy in a Human Prostate Cancer Model (213Bi-DOTA-PESIN and 213Bi-AMBA versus177Lu-DOTA-PESIN)
- 1 February 2011
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (3), 1009-1018
- https://doi.org/10.1158/0008-5472.can-10-1186
Abstract
Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. 213Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-therapy; however, there is limited knowledge available within this context of use. In this study, two novel 213Bi-labeled peptides, DOTA-PEG4-bombesin (DOTA-PESIN) and DO3A-CH2CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA), were compared with 177Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with 177Lu-DOTA-PESIN, 213Bi-DOTA-PESIN, or 213Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive 175Lu-DOTA-PESIN. The MTD of 213Bi-DOTA-PESIN and 213Bi-AMBA was 25 MBq (0.68 mCi) whereas 177Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, 213Bi-DOTA-PESIN and 213Bi-AMBA were significantly more effective than 177Lu-DOTA-PESIN. At the same time, 177Lu-DOTA-PESIN showed minimal, 213Bi-DOTA-PESIN slight, and 213Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with 213Bi-DOTA-PESIN or 213Bi-AMBA is more efficacious than β-therapy. Furthermore, 213Bi-DOTA-PESIN has a better safety profile than 213Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer. Cancer Res; 71(3); 1009–18. ©2011 AACR.Other Versions
This publication has 35 references indexed in Scilit:
- Immunoliposomal Delivery of 213Bi for α-Emitter Targeting of Metastatic Breast CancerCancer Research, 2010
- Treatment of Peritoneal Carcinomatosis by Targeted Delivery of the Radio-Labeled Tumor Homing Peptide 213Bi-DTPA-[F3]2 into the Nucleus of Tumor CellsPLOS ONE, 2009
- Radiation-induced bystander signalling in cancer therapyNature Reviews Cancer, 2009
- Preclinical Evaluation of the α-Particle Generator Nuclide 225Ac for Somatostatin Receptor Radiotherapy of Neuroendocrine TumorsClinical Cancer Research, 2008
- Targeted α-particle radiotherapy with 211At-labeled monoclonal antibodiesNuclear Medicine and Biology, 2007
- Targeted α-therapy: past, present, future?Dalton Transactions, 2007
- 213Bi-[DOTA0, Tyr3]Octreotide Peptide Receptor Radionuclide Therapy of Pancreatic Tumors in a Preclinical Animal ModelClinical Cancer Research, 2006
- Production of Ac-225 from Th-229 for Targeted α TherapyAnalytical Chemistry, 2005
- Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to prostate specific membrane antigen (PSMA): Studies in nude miceThe Prostate, 2003
- Delivery of Molecular Medicine to Solid TumorsScience, 1996