Longitudinal tumor hypoxia imaging with [18F]FAZA-PET provides early prediction of nanoliposomal irinotecan (nal-IRI) treatment activity

Abstract 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. [18F]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