Longitudinal tumor hypoxia imaging with [(18)F]FAZA-PET provides early prediction of nanoliposomal irinotecan (nal-IRI) treatment activity.
BACKGROUND
Non-invasive measurement of tumor hypoxia has demonstrated potential for the evaluation of disease progression, as well as prediction and assessment of treatment outcome. [(18)F]fluoroazomycin arabinoside (FAZA) positron emission tomography (PET) has been identified as a robust method for quantification of hypoxia both preclinically and clinically. The goal of this investigation was to evaluate the feasibility and value of repeated FAZA-PET imaging to quantify hypoxia in tumors that received multi-dose chemotherapy.


METHODS
FAZA-PET imaging was conducted over a 21-day period in a mouse xenograft model of HT-29 human colorectal carcinoma, following multi-dose chemotherapy treatment with irinotecan (CPT-11) or nanoliposomal irinotecan (nal-IRI, MM-398).


RESULTS
Tumors treated with 10 mg/kg nal-IRI maintained significantly lower levels of hypoxia and smaller hypoxic fractions compared to tumors that received 50 mg/kg CPT-11. Specifically, differences in FAZA uptake were detectable 9 days before any significant differences in tumor volume were observed between the treatment groups.


CONCLUSIONS
These findings highlight the potential use of FAZA-PET as an early marker of treatment response following multi-dose chemotherapy.
TECHNA Institute for the Advancement of Technology for Health, University Health Network, 101 College Street, Rm 7-302, Toronto, Ontario, M5G 1L7, Canada. jinzi.zheng@rmp.uhn.on.ca.|Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. jinzi.zheng@rmp.uhn.on.ca.|Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. jinzi.zheng@rmp.uhn.on.ca.
Jinzi
http://orcid.org/0000-0002-7650-3910
J
Zheng
Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA.
Stephan G
SG
Klinz
Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Raquel
R
De Souza
Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA.
Jonathan
J
Fitzgerald
TECHNA Institute for the Advancement of Technology for Health, University Health Network, 101 College Street, Rm 7-302, Toronto, Ontario, M5G 1L7, Canada.|Department of Radiation Physics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.|Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
David A
DA
Jaffray
FAZA; Hypoxia; Irinotecan; Liposome; PET