NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours
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The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [18F]fluoromisonidazole ([18F]FMISO).
[18F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [18F]fluorodeoxyglucose ([18F]FDG) PET scans were also performed in the mice bearing human tumour xenografts.
In 10 out of 11 experimental tumour models, [18F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR75% and TMRR5 (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [18F]FMISO uptake in the tumours. The variability observed in [18F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [18F]FDG and [18F]FMISO images.
This study demonstrates the feasibility and utility of [18F]FMISO for imaging murine tumour models using NanoPET.
KeywordsNanoPET Tumour hypoxia [18F]Fluoromisonidazole [18F]Fluorodeoxyglucose Murine tumour models
We thank Paul M. McSheehy, Terence O’Reilly and Ilse Novak for providing the experimental tumour models at our disposal, Claudia Keller for important help in animal experiments and Erika Sinnig for essential laboratory work. Furthermore, the authors thank Valerie Treyer and Nicolas Späth for fruitful discussions during the writing process.
The Swiss Federal Veterinary Office approved all experimental procedures and all animal work was performed by licensed investigators.
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