Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys.
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.



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.



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.



[(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA. dean.campbell@agensys.com.
Dean O
DO
Campbell
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Akihiro
A
Noda
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Alla
A
Verlinsky
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Josh
J
Snyder
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Yuji
Y
Fujita
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Yoshihiro
Y
Murakami
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Hiroshi
H
Fushiki
Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Sosuke
S
Miyoshi
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Sergio
S
Lacayo
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Edward
E
Cabral
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Peng
P
Yang
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
David R
DR
Stover
Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA.
Ingrid B J K
IB
Joseph
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001859:Bone Neoplasms / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008113:Liver Neoplasms / Q000556:secondary; D008252:Macaca fascicularis; D051379:Mice; D000075983:Nectins; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D015040:Zirconium / Q000737:chemistry
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007202:Indicators and Reagents; D000075983:Nectins; D015040:Zirconium
ImmunoPET; Liver imaging; Nectin-4; Zr-89 PET