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

Fulltext large Open access2  

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
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048713181&doi=10.1186%2fs13550-018-0409-1&partnerID=40&md5=00661e0f9250a193b4709fc52febf5a3
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
MSK Authors
  1. Nagavarakishore Pillarsetty
    70 Pillarsetty
  2. John Laurence Humm
    366 Humm
  3. James Russell
    33 Russell
  4. Louise Marianne Fanchon
    11 Fanchon
  5. Milan Grkovski
    29 Grkovski
Related MSK Work