Development of Preladenant-Based Radiotracers for Imaging A2AR in Tumors

Activation of the adenosine 2A receptor (A_2AR) 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 A_2AR in the tumor. The uptake of radioprobes in A_2AR-negative 4T1 breast tumor was lower than that of A_2AR-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 A_2AR-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.