Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging.
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.
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Xuan
X
Huang
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.|Department of Vascular Medicine, Tianjin Union Medicine Center, Tianjin, China.
Zhongjie
Z
Pan
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Michael L
ML
Doligalski
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.|Department of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Xia
X
Xiao
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Epifanio
E
Ruiz
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Mikalai M
MM
Budzevich
Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Haibin
H
Tian
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000494:pharmacology
D005462:Fluorine Radioisotopes; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals
3-dioxygenase (IDO); PET; [18F]IDO49; immunotherapy; indoleamine 2; novel radioligand