Pharmacokinetics and metabolism of 2-[ 18F]fluoro-2-deoxy- d-glucose (FDG) in mammary tumors of antiestrogen-treated rats

• Published in: Nuclear medicine and biology 1995-05, Vol.22 (4), p.483-489
• Main Authors: Haaparanta, Merja, Paul, Robert, Huovinen, Riikka, Kujari, Harry, Bergman, Jörgen, Solin, Olof, Kangas, Lauri
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Brain - metabolism; Chromatography, High Pressure Liquid; Deoxyglucose - analogs & derivatives; Deoxyglucose - metabolism; Deoxyglucose - pharmacokinetics; Female; Fluorine Radioisotopes - metabolism; Fluorine Radioisotopes - pharmacokinetics; Fluorodeoxyglucose F18; Kinetics; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Myocardium - metabolism; Rats; Rats, Sprague-Dawley; Skin - metabolism; Time Factors; Tissue Distribution
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/0969-8051(94)00121-Y

Attempts are being made to evaluate 2-[ 18F]fluoro-2-deoxy- d-glucose (FDG) as a noninvasive marker of therapy response in malignant tumors. We studied rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinomas by measuring the differential absorption ratio (DAR) and the metabolites of FDG in tumor homogenates. Half the rats were treated with the antiestrogen toremifene for 14 days and half were untreated. The histology of the tumors was studied by morphometry. The animals were killed 15, 45 or 240 min after injection. Regardless of whether the rats received toremifene or not, the fractional change in tumor volume correlated better with the DAR at 15 min [ r = 0.284 (untreated) and r = 0.721 (treated)] and at 240 min [ r = 0.932 (untreated)], than at 45 min [ r = −0.137 (untreated) and r = 0.265 (treated)]. Inverse relations were found for the fraction of unmetabolized FDG and change in tumor volume [ r = 0.070 (45 min) and r = −0.872 (240 min) for untreated tumors and r = −0.963 (15 min) and r = −0.715 (45 min) for treated tumors]. The DAR and the fraction of unmetabolized FDG correlated also [ r = −0.420 (15min), r = −0.647 (45min) and r = −0.976 (240 min) for untreated tumors, and r = −0.963 (15 min) and r = −0.213 (45min) for treated tumors]. No significant therapy-induced morphometrical changes were observed. These findings imply that the FDG-derived uptake of radioactivity (= DAR) does relate to the tumors's speed of growth shortly after injection and also after some time, but there is a time period inbetween (a “twilight zone”) when this correlation is poor. These findings may have implications for FDG-PET studies in cancer patients: the optimal imaging time may have to be reconsidered.