Figure 5. [11C] and [18C]-CHOLINE

Radiolabeled choline (11 C-choline) has been used to study tumor lipid metabolism.

Choline kinase (ChoK) is the first enzyme responsible for the de novo synthesis of phosphatidylcholine (PC), one of the basic lipid components of membranes. ChoK is responsible of the generation of phosphorylcholine (PCho) from its precursor, choline.  

Overexpression of Choline kinase is a frequent event in the development of human cancers. Choline kinase expression has been shown to be associated with certain cell stresses and has also been shown to act as a second messenger in cell growth signaling. Human cancer cells do not store significant amounts of triglycerides but esterify fatty acids to phospholipids, such as phophatidylcholine.

Pharmacokinetics:
The first step of choline accumulation by tumor cells is transport across the cell membrane by various transporters. Since choline is a polar molecule, uptake by passive diffusion is low.
ChoK phosphorylates free choline to phospho-choline (PCho), which represents the first step of choline metabolism. Catalyzed by choline-cytidyltransferase (CCT), PCho can then react with CTP (cytosine triphosphate) to form cytosine diphosphate-choline (CDP-choline). The phosphorylcholine unit of CDP-choline is then transferred to a diacylglycerol (DAG) by cholinephosphotransferase (CPT) to form phosphatidylcholine (PC), a major constituent of the mammalian cell membrane. Intracellular choline levels are determined by both the rate of choline uptake as well as the rate of phosphatidylcholine synthesis and degradation

Urinary excretion of 11 C-choline is markedly lower than that of 18 F-FDG, which facilitates evaluation of primary and recurrent tumors in the pelvis.

- Ramírez de Molina A,  et al. Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochemical and Biophysical Research Communications 2002; 296:580–583
- Plathow C, Weber WA. Tumor Cell Metabolism Imaging; J Nucl Med; 2008;49:43S-63S.