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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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

Fingerprint Dive into the research topics of 'Immunospecific Saturable Clearance Mechanisms for Indium-111-labeled Anti-Melanoma Monoclonal Antibody 96.5 in Humans'. Together they form a unique fingerprint.

Cite this