Immunospecific Saturable Clearance Mechanisms for Indium-111-labeled Anti-Melanoma Monoclonal Antibody 96.5 in Humans

James L. Murray, Lamk M. Lamki, Linda J. Shanken, Mary E. Blake, Carl E. Plager, Robert S. Benjamin, Sally Schweighardt, Michael W. Unger, Michael G. Rosenblum

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18 Citations (Scopus)

Abstract

Liver uptake of 111In-labeled monoclonal antibodies (MoAb) remains a significant problem in radioimaging studies to date. To determine if the observed liver uptake of an 111In-labeled anti-melanoma antibody 96.5 (111In-96.5) was dependent on the presence of hepatic antigen or on recognition of circulating murine antibody, escalating doses of an unlabeled nonimmunoreactive MoAb (NIR-MoAb) were administered to 18 patients with metastatic malignant melanoma either 1 or 24 h prior to an infusion of 1 mg of 111In-96.5. The number of metastases imaged, pharmacokinetics, and the ratio of radioactivity (expressed as average counts/ pixel) in liver (L) spleen (S), bone (B), and kidney (K) compared to blood pool (heart = H) were examined. Results were prospectively compared with data from six patients who received immunoreactive unlabeled 96.5 prior to 111In-965. Increasing dose or changes in the preinfusion time of NIR-MoAb had no significant effect on the biodistribution of 111In-96.5. In contrast, patients who received unlabeled, immunoreactive 96.5 prior to 111In-965 infusion demonstrated a significant drop [P < 0.001] in the liver/heart ratio of radioactivity [251 ± 035 (SEM)] compared to patients receiving the identical dose of NIR-MoAb [1035 ± 133]. Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t2 both decreased when 96.5 was administered compared to NIR-MoAb. In addition, a 4-fold increase in concentration x time was obtained after 96.5 antibody was administered compared to NIR-MoAb. More metastases were imaged in patients receiving preinfusions of 96.5 (23 of 28) than in patients receiving NIR-MoAb (10 of 18; P < 0.05). Although tissue distribution of 111In-labeled antibody can be ascribed to nonspecific organ clearance of murine antibodies, a substantial component of tissue disposition of antibody 96.5 was shown to be a consequence of specific clearance of immunoreactive antibody which may cross-react with tissue antigens.

Original languageEnglish
Pages (from-to)4417-4422
Number of pages6
JournalCancer Research
Volume48
Issue number15
Publication statusPublished - 1988

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Murray, J. L., Lamki, L. M., Shanken, L. J., Blake, M. E., Plager, C. E., Benjamin, R. S., Schweighardt, S., Unger, M. W., & Rosenblum, M. G. (1988). Immunospecific Saturable Clearance Mechanisms for Indium-111-labeled Anti-Melanoma Monoclonal Antibody 96.5 in Humans. Cancer Research, 48(15), 4417-4422.