NanoPET imaging of [(18)F]fluoromisonidazole uptake in experimental mouse tumours.
OBJECTIVE
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 [(18)F]fluoromisonidazole ([(18)F]FMISO).


METHODS
[(18)F]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, [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET scans were also performed in the mice bearing human tumour xenografts.


RESULTS
In 10 out of 11 experimental tumour models, [(18)F]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 TMRR(75%) and TMRR(5) (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 [(18)F]FMISO uptake in the tumours. The variability observed in [(18)F]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 [(18)F]FDG and [(18)F]FMISO images.


CONCLUSIONS
This study demonstrates the feasibility and utility of [(18)F]FMISO for imaging murine tumour models using NanoPET.
Wyss
Matthias T
MT
Center for Radiopharmaceutical Science of ETH, PSI and USZ, Paul Scherrer Institute, Villigen, Switzerland. matthias.wyss@usz.ch
Honer
Michael
M
Schubiger
Pius A
PA
Ametamey
Simon M
SM
D000818:Animals; D015687:Cell Hypoxia; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005240:Feasibility Studies; D005260:Female; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D036103:Nanotechnology / Q000295:instrumentation* / Q000379:methods; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods / Q000662:veterinary; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen