Variables influencing tumor uptake of anti-melanoma monoclonal antibodies radioiodinated using para-iodobenzoyl (PIB) conjugate.
Tumor uptake was examined with respect to antigen expression, time-dependent biodistribution, dose of Mab injected, tumor size, and tumor site (i.e., subcutaneous versus lung or liver metastases). NR-ML-05, 96.5, and P94 showed significantly greater uptake in subcutaneous tumors than CL207 and 5.1 (p less than 0.05). NR-ML-05 had a significantly higher tumor uptake at 24 hr (11.9 +/- 0.51) than at 72 hr (4.0 +/- 0.37) or 144 hr (2.7 +/- 0.84) after injection (p less than 0.001). The other four Mabs had similar tumor distribution at all three time points. The tumor uptake of four Mabs (96.5, P94, CL207. 5.1) differed with respect to in vitro versus in vivo binding to tumor, tumor type, dose of Mab, and tumor site (subcutaneous versus metastases). In contrast, NR-ML-05 demonstrated consistent uptake in tumors independent of the above parameters. These data suggest that certain host parameters can influence in vivo tumor targeting depending on characteristics of each Mab studied.
Murray
J L
JL
Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Mujoo
K
K
Wilmanns
C
C
Mansfield
P
P
Wilbur
D S
DS
Rosenblum
M G
MG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D008545:Melanoma / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes