F-fluoromisonidazole predicts evofosfamide uptake in pancreatic tumor model.

BACKGROUND

Quantitative imaging can facilitate patient stratification in clinical trials. The hypoxia-activated prodrug evofosfamide recently failed a phase III trial in pancreatic cancer. However, the study did not attempt to select for patients with hypoxic tumors. We tested the ability of F-fluoromisonidazole to predict evofosfamide uptake in an orthotopic xenograft model (BxPC3).

METHODS

Two forms of evofosfamide were used: (1) labeled on the active moiety (H) and (2) on the hypoxia targeting nitroimidazole group (C). Tumor uptake of evofosfamide and F-fluoromisonidazole was counted ex vivo. Autoradiography of C and F coupled with pimonidazole immunohistochemistry revealed the spatial distributions of prodrug, radiotracer, and hypoxia.

RESULTS

There was significant individual variation in F-fluoromisonidazole uptake, and a significant correlation between normalized F-fluoromisonidazole and both H-labeled and C-labeled evofosfamide. F-fluoromisonidazole and C-evofosfamide both localized in hypoxic regions as identified by pimonidazole.

CONCLUSION

F-fluoromisonidazole predicts evofosfamide uptake in a preclinical pancreatic tumor model.