Total Choline at 1HMRS and 18FFluoromethylchol

Authors: Sandi Kwee Thomas Ernst

Publish Date: 2010/05/11

Volume: 12, Issue: 4, Pages: 424-425

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Abstract

The use of in vivo imaging techniques for assessing choline metabolism to detect cancer is supported by studies showing increased choline kinase and transporter gene expression transmembrane choline transport and tissue choline metabolite concentration in a number of malignancies 1 2 Early clinical studies employing techniques for in vivo imaging of choline metabolism looked promising with early PET studies demonstrating increased choline tracer uptake in a variety of tumors and independently studies employing proton magnetic resonance spectroscopy 1HMRS demonstrating increased tissue levels of choline metabolites in several malignancies 2 3 4 5 However the use of these two very different in vivo methods to study choline metabolism have raised questions as to how their measurements interrelate and there have been instances where choline tracer uptake on PET fails to correlate well with the tissue measurements of choline provided by 1HMRS 6To address these questions Rommel et al in their study titled “Rodent Rhabdomyosarcoma Comparison Between Total Choline Concentration at 1HMRS and 18Ffluoromethylcholine FCH Uptake at PET Using Accurate Methods for Collecting Data” employed methods for achieving highly accurate spatial correspondence between smallanimal PET and MRI to study the relationship between FCH uptake and spectroscopic measurement of tissue choline metabolites in a rhabdomyosarcoma animal model Their study did not confirm a quantitative relationship between tumor FCH uptake and measures of choline concentration obtained with 1HMRS in their experimental model The authors offered several biological hypotheses to explain the lack of correlation between FCH uptake and choline metabolite concentration one involving the presence of a negative feedback mechanism of elevated levels of intracellular choline compounds on FCH uptake another involving the rapid transport and incorporation of choline into membrane phosphatidylcholine which is not detectable by 1HMRS to explain increases in FCH uptake without corresponding increases in total choline metabolite concentration on 1HMRSIn addition to these biological hypotheses the limited ability of in vivo 1HMRS to discriminate specific choline metabolites may also be worth considering as a potential explanation for their observations Specifically the “choline peak” at 32 ppm that is often used for in vivo 1HMRS studies is known to actually reflect a number of important choline metabolites 7 Ex vivo and in vitro NMR can readily differentiate several of these metabolites bearing the choline moiety They include free choline phosphocholine PC at 323 ppm and glycerophosphocholine GPC at 324 ppm 8 9 However due to their spectral proximity it has proven difficult to resolve these compounds in vivo 2 PC is a predominant biosynthetic product whose concentrations in malignancy can increase as a result of choline kinase upregulation 1 GPC on the other hand is primarily a product of phospholipase activation 10 11 In the study by Rommel et al the inability to separate the spectral contributions of these biochemically distinct compounds should raise the question of whether FCH uptake is actually being compared to the net result of several anabolic and catabolic processes in the CDPcholine pathway Such a situation could potentially explain the lack of correlation observed between total choline concentration and FCH uptakeWork by DeGrado et al has suggested FCH to be a marker of biosynthetic PC metabolism with specificity for the transmembrane choline transporter and choline kinase 12 13 Consequently the tissue concentration of PC rather than total choline may correlate best with FCH uptake The relationship between PC and GPC metabolism under some tumor conditions has been studied For example activation of phospholipase can decrease PC and increase GPC levels in breast and prostate cancer cells potentially leading to a less aggressive phenotype 11 14 Exposure to chemotherapeutic agents can also decrease tissue levels of PC while increasing the levels of GPC 15 16 These results suggest the possibility of assessing tumor therapeutic response through specific measurement of PC or GPC metabolism We look forward to future studies comparing FCH PET to other methods for measuring PC metabolism in vivo

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