Autoradiographic and small-animal PET comparisons between (18)F-FMISO, (18)F-FDG, (18)F-FLT and the hypoxic selective (64)Cu-ATSM in a rodent model of cancer.
BACKGROUND
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.
Dence
Carmen S
CS
Mallinckrodt Institute of Radiology, The Alvin J Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ponde
Datta E
DE
Welch
Michael J
MJ
Lewis
Jason S
JS
D000818:Animals; D001345:Autoradiography; D045744:Cell Line, Tumor; D056831:Coordination Complexes; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D018316:Gliosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000662:veterinary*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013882:Thiosemicarbazones / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D056831:Coordination Complexes; D003301:Copper Radioisotopes; D015224:Dideoxynucleosides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole; C002854:alovudine