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

Abstract 

Introduction

Copper(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.

Methods

Taking advantage of the different half-life of ¹⁸F (t_1/2=110 min) in comparison to ⁶⁴Cu (t_1/2=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.

Results

It 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.

Conclusions

The 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.

Keywords: Hypoxia, Proliferation, Metabolism