Tumor retention of 186Re-MAG3, 111In-DTPA and 125I labeled monoclonal antibody G250 in nude mice with renal cell carcinoma xenografts.
In radioimmunotherapy of solid tumors substantial gain might be achieved by carefully selecting the radionuclide and the linker connecting it to the antibody. In contrast to 131I, radiometals such as 90Y and 111In may be retained in the tumor cell after internalization of the antibody, thereby enhancing the radiation dose to the tumor. The physical properties of 186Re with 1.08 MeV beta-emission (71%) and 137 keV gamma-emission (10%) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s.c. renal cell carcinoma xenografts the biodistribution and the retention in the tumor of 186Re-MAG3 labeled monoclonal antibody (mAb) G250 as compared to 111In-DTPA-G250, to 125I-G250 and to 131I-MN14 (non-specific control mAb). Radiolabeled antibody preparations were i.v. injected. Seventy two hours p.i. the biodistribution of the radiolabel was determined. Blood levels of all mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43% ID/g for 125I, 111In and 186Re respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3% ID/g), indicating tumor processing of mAb G250. Retention of 111In in the tumor was significantly higher than of 186Re and 125I whereas retention in the tumor of 186Re and 125I did not differ significantly.


CONCLUSIONS
In contrast to other radiometals such as 111In and 90Y, 186Re is not retained in the tumor cell. Therefore 186Re has no additional advantage for radioimmunotherapy with respect to retention in the tumor.
Steffens
M G
MG
Department of Urology, University Hospital Nijmegen, The Netherlands. m.steffens@nugen.azn.nl
Kranenborg
M H
MH
Boerman
O C
OC
Zegwaart-Hagemeier
N E
NE
Debruyne
F M
FM
Corstens
F H
FH
Oosterwijk
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012211:Rhenium / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C106533:G250 monoclonal antibody; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C114893:rhenium-mercaptoacetyltriglycine; D012211:Rhenium; D004369:Pentetic Acid