Design, synthesis and evaluation of novel prostate-specific membrane antigen-targeted aryl [18F]fluorosulfate PET tracers

Abstract

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, ¹⁸F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC₅₀ = 1.85-5.15 nM). After the radioisotope exchange labeling, [¹⁸F]L9 and [¹⁸F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [¹⁸F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.

Keywords: Aryl fluorosulfate; Positron emission tomography (PET) imaging; Prostate cancer; Prostate-specific membrane antigen (PSMA).