Abstract
BackgroundNon-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.MethodsFAZA-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).ResultsTumors 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.ConclusionsThese findings highlight the potential use of FAZA-PET as an early marker of treatment response following multi-dose chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0135-x) contains supplementary material, which is available to authorized users.
Highlights
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
Treatment group randomization and baseline FAZA uptake In order to ensure that the response is consistent across animals and tumors that received the same treatment, mice bearing bilateral tumors were randomized into three treatment groups based on pretreatment growth kinetics (Fig. 2a) and caliper-measured tumor volume at treatment day 0 (Fig. 2b)
The differences measured in the baseline mean FAZA muscle uptake among the three treatment groups were relatively small (0.58 ± 0.18 %ID/g for the irinotecan group, 0.78 ± 0.32 %ID/g for the 5 mg/kg nalIRI group, and 0.80 ± 0.18 %ID/g for the 10 mg/kg nalIRI group) and were not statistically significant (p = 0.304)
Summary
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. [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. FAZA-based PET quantification of hypoxia proved to be highly reproducible in untreated animals when imaged 24 h apart [6] Both preclinical and clinical reports have shown encouraging prognostic and predictive power of FAZAPET-based hypoxia imaging, when used in conjunction with radiotherapy [4, 8, 9]. Other PET-based tracers such as [18F]-fluorodeoxygluocose (FDG) and [18F]-fluorothymidine (FLT) have shown potential in predicting early treatment response in patients and animal models of cancer [22, 23], they do not directly provide information on the hypoxia status of a tumor
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