Fig. 1: Overview of choline metabolism and study design.
From: Oral intake of deuterated choline at clinical dose for metabolic imaging of brain tumors
Schematic illustrating choline metabolism in glioma cells, and the differences between IV (A) and oral (per os, PO) (B) administration of 2H9-choline. The 2H9 label, located on the trimethyl group, is highlighted in red on the molecular structures within the glioma cell. Previous studies have indicated increased choline kinase alpha (CKA) activity in cancer cells, thereby rapidly converting Cho compared to the slower conversion of PC to CDP-Cho. We hypothesize that this enzymatic rate difference can be leveraged with serial low PO doses of 2H9-Cho to accumulate a 2H9-PC pool that results in tumor-to-NAB contrast comparable to a single, high IV dose. PO administration implies that 2H9-Cho enters the circulation via the liver, where betaine is synthesized from Cho. Betaine could contribute to the DMI maps; however, it has not been shown to be related to tumor metabolism, and it remains unclear whether betaine is taken up by RG2 glioma cells or remains extracellular. Cho choline, PC phosphocholine, CDP-Cho cytidine diphosphate-choline, PtdCho phosphatidylcholine, GPC glycerophosphocholine, CKA choline kinase alpha. Parts of the figure were adapted from Servier Medical Art, licensed under a Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/).
