A novel PET probe for tumor hypoxia imaging with excellent renal clearance

Objectives PET for detection of tumor hypoxia considerably contributes to the optimization of cancer therapy. Although ¹⁸F-FMISO PET has been performed to detect tumor hypoxia in clinical settings, its excretion rate is too slow to show good contrast between hypoxic tumors and background areas. In this study, we aimed to develop a novel ¹⁸F-labeled PET probe for hypoxia imaging with better renal clearance than ¹⁸F-FMISO.

Methods Our unique probe was designed using pimonidazole, a radiosensitizer with excellent renal clearance. Our new probe was named ¹⁸F-FPINI and was synthesized through the reaction of mesylated pimonidazole with K¹⁸F/K2.2.2. Biodistribution of ¹⁸F-FPINI in C3H/He mice bearing FM3A tumor was compared with that of ¹⁸F-FMISO. Furthermore, their in vivo images were obtained using a PPIS-4800 planar scanner (Hamamatsu Photonics, Japan) for 120 min after intravenous injection.

Results The optimization of the reaction conditions resulted in successful synthesis of ¹⁸F-FPINI with satisfactory radiochemical yield (14%-26%, 80-230 GBq/µmol). ¹⁸F-FPINI showed good tumor retention and rapid renal excretion (63% of the injected dose was excreted in the urine in 2 h). Biodistribution and renal clearance of ¹⁸F-FPINI were more desirable than those of ¹⁸F-FMISO for hypoxia imaging, which was retained in muscle, blood, and other organs for a longer duration. In vivo planar images revealed that ¹⁸F-FPINI clearly depicted tumor hypoxia at an early stage, whereas ¹⁸F-FMISO failed to do so. At 60 min after injection, tumor/muscle (T/M) and tumor/blood (T/B) ratios for ¹⁸F-FPINI were 2.10 and 2.40, respectively, whereas those for ¹⁸F-FMISO were 1.73 and 2.00, respectively.

Conclusions We successfully synthesized a novel PET probe for hypoxia imaging. ¹⁸F-FPINI showed a more rapid renal clearance than the most popular probe ¹⁸F-FMISO. ¹⁸F-FPINI clearly depicted tumor hypoxia. Therefore, ¹⁸F-FPINI would be a promising PET probe for tumor hypoxia