Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys.
Document Type
Journal Article
Author
Campbell, Dean;
Noda, Akihiro;
Verlinsky, Alla;
Snyder, Josh;
Fujita, Yuji;
Murakami, Yoshihiro;
Fushiki, Hiroshi;
Miyoshi, Sosuke;
Lacayo, Sergio;
Cabral, Edward;
Yang, Peng;
Stover, David;
Joseph, Ingrid;
Campbell, Dean O;
Stover, David R;
Joseph, Ingrid B J K
Source
Molecular Imaging & Biology. Oct2016, Vol. 18 Issue 5, p768-775. 8p.
Subject
*NECTINS
*POSITRON emission tomography
*BIOLOGICAL reagents
*TUMORS
*KRA
*DISEASES
*ANIMAL experimentation
*BONE tumors
*CELL adhesion molecules
*CELL lines
*CHEMICAL reagents
*IMMUNOHISTOCHEMISTRY
*LIVER tumors
*METALS
*MICE
*MONOCLONAL antibodies
*PRIMATES
Abstract
Purpose: Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models.Procedures: The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated.Results: A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues.Conclusions: [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions. [ABSTRACT FROM AUTHOR]