3区 · 医学
Article
作者: Yang, Peng ; Snyder, Josh ; Cabral, Edward ; Fushiki, Hiroshi ; Campbell, Dean O ; Stover, David R ; Miyoshi, Sosuke ; Murakami, Yoshihiro ; Joseph, Ingrid B J K ; Lacayo, Sergio ; Verlinsky, Alla ; Noda, Akihiro ; Fujita, Yuji
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.
