Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging

Xuan Huang; Zhongjie Pan; Michael L. Doligalski; Xia Xiao; Epifanio Ruiz; Mikalai M. Budzevich; Haibin Tian

doi:10.18632/oncotarget.14898

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Research Papers:

Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging

Xuan Huang, Zhongjie Pan, Michael L. Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M. Budzevich and Haibin Tian _

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Oncotarget. 2017; 8:46900-46914. https://doi.org/10.18632/oncotarget.14898

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Abstract

Xuan Huang1, Zhongjie Pan1,2, Michael L. Doligalski1, Xia Xiao1,3, Epifanio Ruiz1, Mikalai M. Budzevich1 and Haibin Tian1

1Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

2Department of Vascular Medicine, Tianjin Union Medicine Center, Tianjin, China

3Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, China

Correspondence to:

Haibin Tian, email: [email protected]

Keywords: indoleamine 2,3-dioxygenase (IDO), [¹⁸F]IDO49, PET, novel radioligand, immunotherapy

Received: November 01, 2016 Accepted: December 23, 2016 Published: January 30, 2017

ABSTRACT

IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments. Specific accumulation of the new radiotracer [¹⁸F]IDO49 was observed in IDO1-expressing tumors and confirmed by Western blot and IHC analyses. These results suggest that [¹⁸F]IDO49 has substantial potential as an imaging agent that targets IDO1 in tumors, and therefore may be utilized as a companion diagnostic for IDO1 targeted therapies.

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Research Papers:

Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging

Abstract