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

AbstractAIM:
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.
AuthorsMartin Behe, Karen Alt, Friederike Deininger, Patrick Bühler, Ulrich Wetterauer, Wolfgang A Weber, Ursula Elsässer-Beile, Philipp Wolf
JournalIn vivo (Athens, Greece) (In Vivo) 2011 Jan-Feb Vol. 25 Issue 1 Pg. 55-9 ISSN: 1791-7549 [Electronic] Greece
PMID21282735 (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
  • Glutamate Carboxypeptidase II
  • glutamate carboxypeptidase II, human
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

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