TY - JOUR
T1 - Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts
AU - Kievit, Els
AU - Van Gog, Frank B.
AU - Schlüper, Hennie M M
AU - Van Dongen, Guus A M S
AU - Pinedo, Herbert M.
AU - Boven, Epie
PY - 1997/7/1
Y1 - 1997/7/1
N2 - Purpose: The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of β- particles of a high-energy and a low-abundance of γ-emission. The γ- emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the γ-emission of the widely used radionuclide 131I. In the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3 may be better suited for the treatment of ovarian cancer than 131I-323/A3. Methods and Materials: We compared the biodistribution and the efficacy of 186Re- and 131I- labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate. Results: A molar ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re- and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by 186Re-323/A3 was 1.3- fold higher than that of 131I-323/A3. When mice were treated with equivalent radionuclide doses, the tumor growth inhibition induced by 186Re-323/A3 was similar or slightly better when compared with the efficacy of 131I-323/A3. When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more effective in the inhibition of the growth of FMa and OVCAR-3 xenografts. Conclusions: The favorable physical characteristics of 186Re as well as its efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients.
AB - Purpose: The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of β- particles of a high-energy and a low-abundance of γ-emission. The γ- emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the γ-emission of the widely used radionuclide 131I. In the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3 may be better suited for the treatment of ovarian cancer than 131I-323/A3. Methods and Materials: We compared the biodistribution and the efficacy of 186Re- and 131I- labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate. Results: A molar ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re- and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by 186Re-323/A3 was 1.3- fold higher than that of 131I-323/A3. When mice were treated with equivalent radionuclide doses, the tumor growth inhibition induced by 186Re-323/A3 was similar or slightly better when compared with the efficacy of 131I-323/A3. When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more effective in the inhibition of the growth of FMa and OVCAR-3 xenografts. Conclusions: The favorable physical characteristics of 186Re as well as its efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients.
KW - I
KW - Re
KW - MAb 323/A3
KW - Ovarian cancer xenografts
KW - Radioimmunotherapy
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U2 - 10.1016/S0360-3016(97)00007-2
DO - 10.1016/S0360-3016(97)00007-2
M3 - Article
C2 - 9240651
AN - SCOPUS:0030859197
SN - 0360-3016
VL - 38
SP - 813
EP - 823
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
IS - 4
ER -