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Metabolic positron emission tomography imaging of cancer:Pairing lipid metabolism with glycolysis

         

摘要

The limitations of fluorine-18 fluorodeoxy-D-glucose(FDG)in detecting some cancers has prompted a longstandin search for other positron emission tomography(PET tracers to complement the imaging of glycolysis i oncology, with much attention paid to lipogenesis base on observations that the production of various lipid an lipid-containing compounds is increased in most cancers Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade showing convincingly improved detection sensitivit over FDG for certain cancers. However, neither cholin nor acetate have been thoroughly validated as lipogeni biomarkers, and while acetyl-Co A produced from acetat is used in de-novo lipogenesis to synthesize fatty acids acetate is also consumed by various other syntheti and metabolic pathways, with recent experimenta observations challenging the assumption that lipogenesi is its predominant role in all cancers. Since tumor detected by acetate PET are also frequently detected b choline PET, imaging of choline metabolism might serv as an alternative albeit indirect marker of lipogenesis particularly if the fatty acids produced in cancer cell are mainly destined for membrane synthesis throug incorporation into phosphatidylcholines. Aerobic glycolysi may or may not coincide with changes in lipid metabolism resulting in combinatorial metabolic phenotypes that ma have different prognostic or therapeutic implications Consequently, PET imaging using dual metabolic tracers in addition to being diagnostically superior to imagin with individual tracers, could eventually play a greate role in supporting precision medicine, as efforts t develop small-molecule metabolic pathway inhibitors ar coming to fruition. To prepare for this advent, clinical an translational studies of metabolic PET tracers must g beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated wit these metabolic alterations.

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