Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts.
OBJECTIVE
The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of beta-particles of a high-energy and a low-abundance of gamma-emission. The gamma-emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the gamma-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
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.
Kievit
E
E
Department of Medical Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
van Gog
F B
FB
Schlüper
H M
HM
van Dongen
G A
GA
Pinedo
H M
HM
Boven
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C104214:technetium-99m-MAG3-dsFV; D012211:Rhenium