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- Title
Development of a New Method to Evaluate the Biodistribution of Antibodies Using Non-Radioactive Metal Labeling and Inductively Coupled Plasma Mass Spectrometry.
- Authors
Nagayasu, Miho; Takano, Yoko; Ozeki, Kazuhisa
- Abstract
Purpose: The use of radiolabeled compounds is associated with a number of limitations. Therefore, a new method for the radioisotope-free evaluation of antibody distribution using metal labeling and inductively coupled plasma-mass spectrometry (ICP-MS) was developed herein. Methods: Indium-labeled monoclonal antibodies were administrated intravenously to tumor-bearing mice and cynomolgus monkeys, and antibody concentrations in plasma and tissues were measured by ICP-MS. The results were compared with those obtained using a ligand binding assay (LBA) and radioisotope-labeled antibody administration. Indium-, terbium-, holmium-, and yttrium-labeled cetuximab were co-administered to one C57BL/6 J mouse for simultaneous PK and tissue distribution evaluations. Results: The administration of a radioactive or non-radioactive indium-labeled anti-human interleukin-6 receptor (hIL-6R) antibody to tumor-bearing hIL-6R transgenic mice resulted in similar plasma antibody concentration-time profiles by ICP-MS, a ligand binding assay (LBA), and gamma-ray detector. Liver, kidney, brain, spleen, and tumor concentrations of antibodies measured by ICP-MS were similar to those after the administration of radiolabeled anti-hIL-6R antibodies. Following the administration of indium-labeled cetuximab to cynomolgus monkeys, plasma antibody concentrations measured by ICP-MS were similar to those measured by LBA, and antibody concentrations in organs were evaluable by ICP-MS. The PK of all metals were similar to antibody PK evaluated by LBA, and concentrations in each tissue were equivalent among metals. Conclusions: The assessment of antibody distribution using ICP-MS is a novel alternative to the traditional radiolabeled approach. It facilitates the assessment of antibody distribution in the early stages of drug discovery and accelerates the assessment of target engagement.
- Subjects
INDUCTIVELY coupled plasma mass spectrometry; INTERLEUKIN-6 receptors; IMMUNOGLOBULINS; DRUG discovery
- Publication
Pharmaceutical Research, 2023, Vol 40, Issue 7, p1807
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-023-03541-w