Comparison of 131I- and 90Y-labeled monoclonal antibody 17-1A for treatment of human colon cancer xenografts.
The choice of radionuclide remains an important question in clinical radioimmunotherapy. Therefore, a study was initiated, using an in vivo model system, to assess the relative merits of 131I- and 90Y-labeled 17-1A monoclonal antibody as therapeutic agents in the treatment of colon cancer. 131Iodine- and 90Y-labeled 17-1A were assessed in animal therapy trials using athymic nude mice bearing LS174T human colon cancer xenografts. 131Iodine-labeled 17-1A decreased tumor growth in a dose-dependent fashion without lethality. In contrast, the doses of 90Y-labeled 17-1A which were required to produce a significant increase in tumor doubling time also caused marked toxicity. Although similar tumor growth inhibition was produced by 250 microCi 90Y- and 150 microCi 131I-labeled 17-1A, Medical Internal Radiation Dose calculations based on biodistribution data estimated that the dose delivered by 90Y was greater than that delivered by 131I. To investigate this discrepancy, 3-dimensional dose distributions within LS174T tumors were assessed using autoradiography and 3-dimensional calculational techniques. It was found that a greater fraction of the dose was deposited in the tumor after treatment with 131I- compared to 90Y-labeled 17-1A. When the Medical Internal Radiation Dose calculations were adjusted using the 3-dimensional dose distributions, 250 microCi of 90Y- and 150 microCi of 131I-labeled 17-1A were found to deliver similar tumor doses. These studies suggest that 131I-labeled 17-1A is superior to 90Y-labeled 17-1A, since 131I-labeled antibody produced less hematological and animal toxicity and was more effective at inhibiting LS174T tumor growth than 90Y-labeled antibody across the range of radionuclide doses tested. Furthermore, they suggest that it will be necessary to perform 3-dimensional dose calculations in addition to Medical Internal Radiation Dose calculations in order to interpret tumor dosimetry.
Buchsbaum
D J
DJ
Department of Radiation Oncology, University of Alabama, Birmingham 35233.
Lawrence
T S
TS
Roberson
P L
PL
Heidorn
D B
DB
Ten Haken
R K
RK
Steplewski
Z
Z
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography / Q000379:methods; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes