Autoradiographic and small-animal PET comparisons between 18F-FMISO, 18F-FDG, 18F-FLT and the hypoxic selective 64Cu-ATSM in a rodent model of cancer

IntroductionCopper(II)-diacetyl-bis(N4-methylthiosemicarbazone), or Cu-ATSM, a hypoxia imaging agent, has been shown to be predictive of response to traditional cancer therapies in patients with a wide range of tumors. It is known that the environment of the tumor results in a myriad of physiological consequences, including hypoxia, alterations in metabolism and proliferation. In an effort to better characterize the relationships between Cu-ATSM and other prominent radiopharmaceuticals, this current study was undertaken to compare the regional distribution of 64Cu-ATSM with [18F]fluoromisonidazole (18F-FMISO), [18F]fluoro-2-deoxy-d-glucose (18F-FDG) and [18F]fluorothymidine (18F-FLT) in 9L tumors.MethodsTaking advantage of the different half-life of 18F (t1/2=110 min) in comparison to 64Cu (t1/2=12.7 h), we undertook a dual-tracer autoradiography study in 9L tumors. Four groups were examined: (a) 18F-FMISO, 2 h postinjection (p.i.) and 64Cu-ATSM, 10 min p.i.; (b) 18F-FMISO, 2 h p.i. and 64Cu-ATSM, 24 h p.i.; (c) 18F-FDG, 1 h p.i. and 64Cu-ATSM, 10 min p.i.; and (d) 18F-FLT, 1 h p.i. and 64Cu-ATSM, 10 min p.i. Small-animal PET imaging was performed in 9L tumor-bearing rats with imaging on concurrent days comparing 64Cu-ATSM with 18F-FMISO and 18F-FLT.ResultsIt was shown that the regional distribution of 18F-FMISO and 64Cu-ATSM showed an excellent correlation when the 64Cu-ATSM had been allowed to distribute for either 10 min (R2=.84) or 24 h (R2=.86). The regional comparisons between 64Cu-ATSM (10 min) and 18F-FDG (1 h) resulted in a very poor correlation (R2=.08) between the regional uptake of the two agents. The comparison between 18F-FLT and 64Cu-ATSM showed a strong relationship (R2=.83) between the two tracers. The small-animal PET images for the distribution comparisons between 64Cu-ATSM and 18F-FMISO and 18F-FLT were in agreement with the data generated from the autoradiography studies.ConclusionsThe data show that it is important to remember that a number of different metabolic situations can exist when considering the relationship between regions of high glucose uptake, proliferation and hypoxia.