INTRODUCTION: Copper(II)-diacetyl-bis(N(4)-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 (64)Cu-ATSM with [(18)F]fluoromisonidazole ((18)F-FMISO), [(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) and [(18)F]fluorothymidine ((18)F-FLT) in 9L tumors. METHODS: Taking advantage of the different half-life of (18)F (t(1/2)=110 min) in comparison to (64)Cu (t(1/2)=12.7 h), we undertook a dual-tracer autoradiography study in 9L tumors. Four groups were examined: (a) (18)F-FMISO, 2 h postinjection (p.i.) and (64)Cu-ATSM, 10 min p.i.; (b) (18)F-FMISO, 2 h p.i. and (64)Cu-ATSM, 24 h p.i.; (c) (18)F-FDG, 1 h p.i. and (64)Cu-ATSM, 10 min p.i.; and (d) (18)F-FLT, 1 h p.i. and (64)Cu-ATSM, 10 min p.i. Small-animal PET imaging was performed in 9L tumor-bearing rats with imaging on concurrent days comparing (64)Cu-ATSM with (18)F-FMISO and (18)F-FLT. RESULTS: It was shown that the regional distribution of (18)F-FMISO and (64)Cu-ATSM showed an excellent correlation when the (64)Cu-ATSM had been allowed to distribute for either 10 min (R(2)=.84) or 24 h (R(2)=.86). The regional comparisons between (64)Cu-ATSM (10 min) and (18)F-FDG (1 h) resulted in a very poor correlation (R(2)=.08) between the regional uptake of the two agents. The comparison between (18)F-FLT and (64)Cu-ATSM showed a strong relationship (R(2)=.83) between the two tracers. The small-animal PET images for the distribution comparisons between (64)Cu-ATSM and (18)F-FMISO and (18)F-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.
INTRODUCTION:Copper(II)-diacetyl-bis(N(4)-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 (64)Cu-ATSM with [(18)F]fluoromisonidazole ((18)F-FMISO), [(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) and [(18)F]fluorothymidine ((18)F-FLT) in 9L tumors. METHODS: Taking advantage of the different half-life of (18)F (t(1/2)=110 min) in comparison to (64)Cu (t(1/2)=12.7 h), we undertook a dual-tracer autoradiography study in 9L tumors. Four groups were examined: (a) (18)F-FMISO, 2 h postinjection (p.i.) and (64)Cu-ATSM, 10 min p.i.; (b) (18)F-FMISO, 2 h p.i. and (64)Cu-ATSM, 24 h p.i.; (c) (18)F-FDG, 1 h p.i. and (64)Cu-ATSM, 10 min p.i.; and (d) (18)F-FLT, 1 h p.i. and (64)Cu-ATSM, 10 min p.i. Small-animal PET imaging was performed in 9L tumor-bearing rats with imaging on concurrent days comparing (64)Cu-ATSM with (18)F-FMISO and (18)F-FLT. RESULTS: It was shown that the regional distribution of (18)F-FMISO and (64)Cu-ATSM showed an excellent correlation when the (64)Cu-ATSM had been allowed to distribute for either 10 min (R(2)=.84) or 24 h (R(2)=.86). The regional comparisons between (64)Cu-ATSM (10 min) and (18)F-FDG (1 h) resulted in a very poor correlation (R(2)=.08) between the regional uptake of the two agents. The comparison between (18)F-FLT and (64)Cu-ATSM showed a strong relationship (R(2)=.83) between the two tracers. The small-animal PET images for the distribution comparisons between (64)Cu-ATSM and (18)F-FMISO and (18)F-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.
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Authors: Paul Burgman; Joseph A O'Donoghue; Jason S Lewis; Michael J Welch; John L Humm; C Clifton Ling Journal: Nucl Med Biol Date: 2005-08 Impact factor: 2.408
Authors: A S Kennedy; J A Raleigh; G M Perez; D P Calkins; D E Thrall; D B Novotny; M A Varia Journal: Int J Radiat Oncol Biol Phys Date: 1997-03-01 Impact factor: 7.038
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Authors: Neale S Mason; Brian J Lopresti; James Ruszkiewicz; Xinxin Dong; Sonali Joyce; George Leef; Malabika Sen; Abdus S Wahed; Chester A Mathis; Jennifer R Grandis; Sufi M Thomas Journal: Am J Nucl Med Mol Imaging Date: 2013-01-05