(18)F-fluoromisonidazole predicts evofosfamide uptake in pancreatic tumor model Journal Article

Authors: Grkovski, M.; Fanchon, L.; Pillarsetty, N. V. K.; Russell, J.; Humm, J. L.
Article Title: (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. © 2018, The Author(s).
Keywords: hypoxia; pancreatic cancer; personalized medicine; 18f-fluoromisonidazole; evofosfamide
Journal Title: EJNMMI Research
Volume: 8
ISSN: 2191-219X
Publisher: Springer  
Date Published: 2018-06-18
Start Page: 53
Language: English
DOI: 10.1186/s13550-018-0409-1
PROVIDER: scopus
PMCID: PMC6005997
PUBMED: 29916085
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. John Laurence Humm
    366 Humm
  2. James Russell
    33 Russell
  3. Louise Marianne Fanchon
    11 Fanchon