E. Kievit et al., [RE-186]-LABELED MOUSE AND CHIMERIC MONOCLONAL-ANTIBODY 323 A3 - A COMPARISON OF THE EFFICACY IN EXPERIMENTAL HUMAN OVARIAN-CANCER/, Nuclear medicine and biology, 25(1), 1998, pp. 37-45
We have investigated whether [Re-186]-labeled chimeric monoclonal anti
body 323/A3 (MAb c-323/A3) is as effective as [Re-186]-labeled mouse 3
23/A3 (m-323/A3) in the growth inhibition of human ovarian cancer xeno
grafts OVCAR-3 and FMa. [Re-186] was conjugated to MAbs with the use o
f the chelate S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3). The
maximum number of metal-MAG3 groups that could be conjugated to one MA
b molecule accepting a minimal initial increase of the blood clearance
(15%) was 8.5 and 2.9 for c-323/A3 and m-323/A3, respectively. With t
hese molar ratios the immunoreactivity of both MAbs was maintained. An
inverse relationship was observed between the protein dose of c-323/A
3 and its blood clearance. Both [Re-186]-c-323/A3 and [Re-186]-m-323/A
3 were comparable in the inhibition of the tumor growth when higher pr
otein doses were used. Together with the expected lower immunogenicity
, our results imply that c-323/A3 is preferable for use in [Re-186]-ra
dioimmunotherapy in ovarian cancer patients. (C) 1998 Elsevier Science
Inc.