Comparison of 18F-FDG, 18F-FET and 18F-FLT for differentiation between tumor and inflammation in rats.

INTRODUCTION: The goal of this study was to compare the glucose analog, 2-[18F]fluoro-2-deoxy-d-glucose ([18F]-FDG), the amino acid analog, o-(2-[18F]fluoroethyl)-l-tyrosine ([18F]-FET) and nucleoside analog, 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) with regard to their feasibility for differentiating tumors from inflammation. METHODS: In Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [18F]-FDG, [18F]-FET and [18F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [18F]-FLT was performed. RESULTS: The tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [18F]-FDG were significantly higher than those of [18F]-FET and [18F]-FLT (P<.01); however, the accumulation of [18F]-FDG [1.23+/-0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [18F]-FET (2.3+/-0.5 and 2.2+/-0.5) were higher than those of [18F]-FLT (1.6+/-0.6 and 1.6+/-0.5), and inflammation uptake of those tracers was very low (0.63+/-0.19 and 0.27+/-0.16 %ID/g, respectively). [18F]-FET and [18F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [18F]-FDG. In PET images, [18F]-FDG was found to be accumulated in both tumor and inflammation, but [18F]-FET and [18F]-FLT selectively localized in tumor. CONCLUSION: Our data confirm the result of previous studies that [18F]-FET and [18F]-FLT are superior to [18F]-FDG in differentiating tumor from inflammation.

Cellular metabolic responses of PET radiotracers to (188)Re radiation in an MCF7 cell line containing dominant-negative mutant p53.

UNLABELLED: We investigated the relations between the cell uptakes of metabolic radiotracers and beta-radiation pretreatment using a dominant mutant p53 (p53mt) cell line to evaluate the effects of p53 genes on (18)F labeled positron emission tomography (PET) radiotracer uptakes. METHODS: pCMV-Neo-Bam (control), which contains a neo-resistance marker, and p53 dominant-negative mutant expression constructs were stably transfected into MCF7 cell line. Cells were plated in 24-well plates at 1.0x10(5) cells for 18 h. Rhenium-188 ((188)Re) (a beta emitter) was added to the medium (3.7, 18.5, 37 MBq) and incubated for 24 h. We performed gamma-counting to determine the cellular uptakes of 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG), o-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) and 2'-[(18)F]fluoro-2'-deoxythymidine (FLT) (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and flow cytometry. RESULTS: p53mt cells showed 1.5-2-fold higher FDG uptake than wild-type p53 cells in basal condition, and the difference of FDG uptake was greater after (188)Re treatment (P<.01). FET uptake increased with (188)Re dose without a significant difference between p53 statuses. p53mt cells showed lower FLT uptake than wild-type p53 cells in basal condition, and the difference of FLT uptake was greater after (188)Re treatment. By cell viability testing and FACS analysis, p53mt cells showed lower viability and a larger apoptotic fraction (sub-G1) than wild-type p53 cells after (188)Re treatment. CONCLUSION: We speculate that p53 dysfunction increases glucose and decreases thymidine metabolism in cancer cells and that this may be exaggerated by (188)Re beta-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after (188)Re beta-radiation treatment, whereas FLT could be a more useful PET radiotracer for assessing therapeutic response to beta-radiation, especially in cancer cells with an altered function of p53.

In vivo comparison of IVDU and IVFRU in HSV1-TK gene expressing tumor bearing rats.

(E)-5-(2-Iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) are potential substrates of Herpes Simplex Virus type 1 thymidine kinase (HSV-TK). In the present study, cellular uptake of radioiodinated substrates was found to be low in wild type MCA cells, but high in HSV-TK gene expressing cells. The carrier-free substrates, in particular, showed higher cellular uptake than carrier-added compounds. Biodistribution showed that the %ID/g of the MCA-TK/MCA tumor ratio of IVDU injected at 1, 4, and 24h were 1.1, 0.9 and 1.3, and those of IVFRU were 1.7, 1.7 and 1.8 respectively. Therefore, both IVDU and IVFRU could possibly be used as radiopharmaceuticals to evaluate reporter gene expression. However, IVFRU was more specific and stable than IVDU for selective non-invasive imaging of HSV-TK expression.