Development of Preladenant-Based Radiotracers for Imaging A 2A R in Tumors.

Activation of the adenosine 2A receptor (A 2A R) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18 F-labeled probes ([ 18 F]F-PFP 2 and [ 18 F]F-PFP 4 ) to visualize A 2A R in the tumor. The uptake of radioprobes in A 2A R-negative 4T1 breast tumor was lower than that of A 2A R-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 [ 18 F]F-PFP 2 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 [ 18 F]F-PFP 2 might lay the foundation for establishing an A 2A R-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.