In vivo testing of 177Lu-labelled anti-PSMA antibody as a new radioimmunotherapeutic agent against prostate cancer.

Abstract

AIM:

The goal of the present study was to test the (177)Lu-labelled anti-PSMA monoclonal antibody 3/F11 ((177)Lu-DOTA-3/F11) as a new radioimmunotherapeutic agent in a prostate cancer SCID mouse xenograft model.

MATERIALS AND METHODS:

The mAb 3/F11 was (177)Lu labelled using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as chelating agent. DOTA-3/F11 was tested for cell binding and serum immunoreactivity by flow cytometry. The biodistribution and the therapeutic efficacy of (177)Lu-DOTA-3/F11 in mice bearing PSMA-positive C4-2 prostate cancer xenografts were evaluated.

RESULTS:

3/F11 and DOTA-3/F11 showed high and specific cell binding and similar serum half-lives of approximately seven days. Biodistribution studies revealed an increasing tumour uptake of (177)Lu DOTA-3/F11 over time with maximum tumour-to-muscle and tumour-to-blood ratios after 72 h. A single dose of 1 MBq (177)Lu-DOTA-3/F11 inhibited tumour growth and prolonged survival.

CONCLUSION:

This study indicated that (177)Lu-DOTA-3/F11 may be a suitable radioimmunotherapeutic agent for the treatment of prostate cancer.

• Authors: Martin Behe, Karen Alt, Friederike Deininger, Patrick Bühler, Ulrich Wetterauer, Wolfgang A Weber, Ursula Elsässer-Beile, Philipp Wolf
• Journal: In vivo (Athens, Greece) (In Vivo) 2011 Jan-Feb Vol. 25 Issue 1 Pg. 55-9 ISSN: 1791-7549 [Electronic] Greece
• PMID: 21282735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 177Lu-DOTA-3-F11
• Antibodies, Monoclonal
• Antigens, Surface
• Coordination Complexes
• Radioisotopes
• Lutetium
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antigens, Surface (immunology)
• Cell Line, Tumor
• Coordination Complexes (therapeutic use)
• Glutamate Carboxypeptidase II (immunology)
• Humans
• Isotope Labeling
• Lutetium (therapeutic use)
• Male
• Mice
• Mice, SCID
• Prostatic Neoplasms (radiotherapy)
• Radioimmunotherapy (methods)
• Radioisotopes
• Xenograft Model Antitumor Assays