Tumor hypoxia is a major contributor to therapeutic resistance, including radio-, chemo-, and immunotherapy, and is closely linked to unfavorable clinical outcomes. PET imaging has shown promise in guiding the clinical treatment of hypoxic tumors. Here, we developed an NTR-responsive PET strategy for in vivo tumor hypoxia imaging using radiolabeled nitrogen mustard analogues (18F-NTRP and 18F-NCRP). Cell uptake studies with A549 cells showed that 18F-NTRP and 18F-NCRP exhibited approximately two fold higher uptake and good retention under hypoxic conditions. MicroPET imaging of A549 tumor-bearing mice revealed pronounced tumor accumulation of both 18F-NTRP and 18F-NCRP, with uptake values of 1.95 ± 0.37 and 2.86 ± 0.49 %ID/g, respectively, and a rapid clearance rate in normal organs. At 45 min postinjection, the tumor/muscle (T/M) ratios of 18F-NTRP and 18F-NCRP were 2.62 and 3.44, respectively, both substantially higher than that of 18F-FMISO (1.40, p 18F-NCRP were decreased to 1.25 ± 0.32 %ID/g and 1.26 (p 2 = 0.71) and NTR (r2 = 0.66) levels in the A549 tumor. Collectively, PET imaging demonstrated that 18F-NCRP specifically targets tumor NTR and can potentially discriminate between varying degrees of hypoxia.
Huang et al. (Wed,) studied this question.