Oncotarget

Research Papers:

Assessment of near-infrared fluorophores to study the biodistribution and tumor targeting of an IL13 receptor α2 antibody by fluorescence molecular tomography

Parul Gupta, Jo-Ann Wentland, Mauricio Leal, Dangshe Ma, Rachel Roach, Antonio Esparza, Lindsay King, Mary E. Spilker, Cedo Bagi, Christopher T. Winkelmann and Anand Giddabasappa _

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Oncotarget. 2017; 8:57231-57245. https://doi.org/10.18632/oncotarget.19569

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Abstract

Parul Gupta1, Jo-Ann Wentland2, Mauricio Leal2, Dangshe Ma3,6, Rachel Roach4, Antonio Esparza5, Lindsay King2, Mary E. Spilker2, Cedo Bagi1, Christopher T. Winkelmann1 and Anand Giddabasappa1

1Global Science and Technology, Comparative Medicine, Pfizer, Inc., La Jolla, CA, USA

2Pharmacokinetics and Drug Metabolism, Pfizer, Inc., New York NY, USA

3Oncology Research Unit, Pfizer, Inc., Pearl River, NY, USA

4Center for Therapeutic Innovation, Pfizer, Inc., La Jolla, CA, USA

5Comparative Medicine, Pfizer, Inc., La Jolla, CA, USA

6Current affiliation: Regeneron Pharmaceuticals, Tarrytown, NY, USA

Correspondence to:

Anand Giddabasappa, email: [email protected]

Keywords: biotherapeutics, tumor targeting, biodistribution, fluorescence molecular tomography (FMT), molecular imaging

Received: January 16, 2017     Accepted: July 03, 2017     Published: July 26, 2017

ABSTRACT

Non-invasive imaging using radiolabels is a common technique used to study the biodistribution of biologics. Due to the limited shelf-life of radiolabels and the requirements of specialized labs, non-invasive optical imaging is an attractive alternative for preclinical studies. Previously, we demonstrated the utility of fluorescence molecular tomography (FMT) an optical imaging modality in evaluating the biodistribution of antibody-drug conjugates. As FMT is a relatively new technology, few fluorophores have been validated for in vivo imaging. The goal of this study was to characterize and determine the utility of near-infrared (NIR) fluorophores for biodistribution studies using interleukin-13 receptor subunit alpha-2 antibody (IL13Rα2-Ab). Eight fluorophores (ex/em: 630/800 nm) with an N-hydroxysuccinimide (NHS) linker were evaluated for Ab conjugation. The resulting antibody-fluorophore (Ab-F) conjugates were evaluated in vitro for degree of conjugation, stability and target-binding, followed by in vivo/ex vivo FMT imaging to determine biodistribution in a xenograft model. The Ab-F conjugates (except Ab-DyLight800) showed good in vitro stability and antigen binding. All Ab-F conjugates (except for Ab-BOD630) resulted in a quantifiable signal in vivo and had similar biodistribution profiles, with peak tumor accumulation between 6 and 24 h post-injection. In vivo/ex vivo FMT imaging showed 17–34% ID/g Ab uptake by the tumor at 96 h. Overall, this is the first study to characterize the biodistribution of an Ab using eight NIR fluorophores. Our results show that 3-dimensional optical imaging is a valuable technology to understand biodistribution and targeting, but a careful selection of the fluorophore for each Ab is warranted.


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