18 F-fluoromisonidazole predicts evofosfamide uptake in pancreatic tumor model

Abstract

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 ¹⁸F-fluoromisonidazole to predict evofosfamide uptake in an orthotopic xenograft model (BxPC3).

Methods

Two forms of evofosfamide were used: (1) labeled on the active moiety (³H) and (2) on the hypoxia targeting nitroimidazole group (¹⁴C). Tumor uptake of evofosfamide and ¹⁸F-fluoromisonidazole was counted ex vivo. Autoradiography of ¹⁴C and ¹⁸F coupled with pimonidazole immunohistochemistry revealed the spatial distributions of prodrug, radiotracer, and hypoxia.

Results

There was significant individual variation in ¹⁸F-fluoromisonidazole uptake, and a significant correlation between normalized ¹⁸F-fluoromisonidazole and both ³H-labeled and ¹⁴C-labeled evofosfamide. ¹⁸F-fluoromisonidazole and ¹⁴C-evofosfamide both localized in hypoxic regions as identified by pimonidazole.

Conclusion

¹⁸F-fluoromisonidazole predicts evofosfamide uptake in a preclinical pancreatic tumor model.

https://ift.tt/2yiGysT