Pharmacokinetics of an indium-labeled IgG monoclonal antibody over a prolonged period

Abstract

This study was directed toward determining the pharmacokinetic fate of an IgG2a monoclonal antibody (MoAb). The 96.5 anti-melanoma MoAb was labeled with indium-111 and indium-114m and administered to BALB/c mice. The mice receiving 111In MoAb were sacrificed at 4 and 72 h, while those receiving 114mIn 96.5 MoAb (50-day physical half-life) were sacrificed at 4 h and 3, 15, and 30 days. Multiple tissues were counted against a standard of the injectate and the data expressed as percent injected dose per organ and percent total dose excreted in the urine and feces. The 111In- and 114mIn-labeled MoAbs had nearly identical distribution through 72 h. Over the 30-day period 25% of the 114mIn label was excreted in the urine and 50% eliminated in the feces. All of the tissues studied showed a decrease in 114mIn in the 30-day period. We conclude that the metabolic products of indium-labeled MoAbs, the indium itself, or a combination of both are eliminated from the tissues over a period of several weeks and do not accumulate to a significant extent in any single site.

Evaluation of the Human Melanoma Targeting Properties of Radiolabeled α-Melanocyte Stimulating Hormone Peptide Analogues

“…Radiolabeled antibodies and antibody fragments have been investigated extensively to target melanoma and its metastases ( − ). However, their success has been limited because of the intrinsic limitations of radiolabeled antibodies and antibody fragments, such as slow circulation clearance ( , ) and reduced rates of tumor penetration ( , ). Recently, 123 I-labeled N -(2-diethylaminoethyl)-4-iodobenzamide ([ 123 I]BZA) and N -(2-diethylaminoethyl)-3-iodo-4-methoxybenzamide ([ 123 I]IMBA) have exhibited high tumor uptake value ranging from 5 to 20 %ID/g in B16 tumor model ( , ).…”

Novel, Cysteine-Modified Chelation Strategy for the Incorporation of [MI(CO)3]+ (M = Re, 99mTc) in an α-MSH Peptide

“…34 Unfortunately, many of these agents have met with limited success due to their antigenicity, 35 reduced rates of tumor penetration, 36 and slow circulation. 37 α-melanocyte stimulating hormone (α-MSH) peptide analogues, which target the melanocortin 1 receptor (MC1R) on melanoma cells, are an emerging class of molecular agents with promise for imaging and treating metastatic melanoma.…”

“…The latter factor results mainly from limitations in the early detection and treatment of melanoma metastases. − Identification of melanoma cell signaling pathways and biomarkers in recent years has allowed the development of molecular imaging agents such as radiolabeled antibodies and antibody fragments for diagnosing melanoma metastases at earlier stages . Unfortunately, many of these agents have met with limited success due to their antigenicity, reduced rates of tumor penetration, and slow circulation . α-Melanocyte stimulating hormone (α-MSH) peptide analogues, which target the melanocortin 1 receptor (MC1R) on melanoma cells, are an emerging class of molecular agents with promise for imaging and treating metastatic melanoma.…”