Development of Preladenant-Based Radiotracers for Imaging A2AR in Tumors

• Published in: Journal of medicinal chemistry 2024-08, Vol.67 (15), p.13056-13066
• Main Authors: Zeng, Xueyuan, Liu, Hongwu, Huang, Guolong, Wang, Yanjie, Zhou, Wuhao, Wang, Yike, Chen, Xuedong, Cheng, Xingxing, Zhuang, Rongqiang, Li, Jindian, Fang, Jianyang, Huang, Lumei, Zhang, Xianzhong, Guo, Zhide
• Format: Article
• Language: English
• ISSN: 0022-2623; 1520-4804; 1520-4804
• DOI: 10.1021/acs.jmedchem.4c01015

Activation of the adenosine 2A receptor (A2AR) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18F-labeled probes ([18F]­F-PFP2 and [18F]­F-PFP4) to visualize A2AR in the tumor. The uptake of radioprobes in A2AR-negative 4T1 breast tumor was lower than that of A2AR-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [18F]­F-PFP2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [18F]­F-PFP2 might lay the foundation for establishing an A2AR-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.