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

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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 [89Zr]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 [18F]AGS-22M6 in cynomolgus monkeys was evaluated.

Results

A positive correlation was demonstrated between tumor nectin-4 expression and [89Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [18F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues.

Conclusions

[89Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

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Authors and Affiliations

  1. Agensys Inc., an affiliate of Astellas Pharma Inc., 1800 Stewart St, Santa Monica, CA, 90404, USA

    Dean O. Campbell, Alla Verlinsky, Josh Snyder, Sergio Lacayo, Edward Cabral, Peng Yang, David R. Stover & Ingrid B. J .K. Joseph

  2. Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan

    Akihiro Noda, Yuji Fujita, Yoshihiro Murakami, Hiroshi Fushiki & Sosuke Miyoshi

Authors
  1. Dean O. Campbell
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  2. Akihiro Noda
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  3. Alla Verlinsky
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  4. Josh Snyder
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  5. Yuji Fujita
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  6. Yoshihiro Murakami
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  8. Sosuke Miyoshi
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  9. Sergio Lacayo
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  10. Edward Cabral
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  11. Peng Yang
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  13. Ingrid B. J .K. Joseph
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Correspondence to Dean O. Campbell.

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Campbell, D.O., Noda, A., Verlinsky, A. et al. Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys. Mol Imaging Biol 18, 768–775 (2016). https://doi.org/10.1007/s11307-016-0953-x

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  • DOI: https://doi.org/10.1007/s11307-016-0953-x

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