[11C]Choline PET

Choline is a precursor for the biosynthesis of phospholipids which are the essential components of all cell membranes (Krohn, 2001). Choline is transported into the cell, phosphorylated by choline kinase to phosphocholine, and further converted to phosphatidylcholine. Choline kinase is expressed in all cells, but overexpressed in cancer cells.

Choline is an endogenous activator of σ1 receptors, potentiating the Ca2+-release in endoplasmic reticulum (Brailoiu et al., 2019).

Acetylcholine (ACh) is the neurotransmitter of cholinergic system. ACh is synthesized from choline and acetyl-CoA by choline acetyltransferase in the presynaptic cholinergic neurons.

[Methyl-11C]choline ([11C]choline) is used as a marker for cellular proliferation in PET imaging.

Choline C-11 labelled choline C-11 labelled betaine

Choline, [11C]choline, and main metabolite [11C]betaine.

Input function

Intact [11C]choline represents 62% ± 19% of the total radioactivity in arterial plasma at 5 min after injection and 27% ± 12% at 15 min; the major metabolite in plasma is [11C]betaine (Roivainen et al., 2000).

Plasma-to-blood ratio of [18F]choline in mice starts from ∼1.7, decreasing rapidly to ∼ 1.1; the ratio curve was be described with function

by Slaets and De Vos (2013).

Tumours

Usefulness of [11C]choline in the tumour diagnosis has been demonstrated (Hara 2002), and quantification by using Patlak plot (MTGA for irreversibly binding tracers), and SUV in clinical setting have been validated (Utriainen et al., 2003; Sutinen et al., 2004). However, cell proliferation may not explain the uptake of [11C]choline in certain cancers (Breeuwsma et al., 2005).

11C- and 18F-labelled choline are well-suited to imaging tumours of bladder and at the pelvic region, because the radioactivity in urine is minimal. Choline PET SUV can improve mpMRI classification in prostate cancer (Gatidis et al., 2015). [18F]fluorocholine PET is superior to [99mTc]sestamibi imaging for detection of parathyroid adenomas (Hope et al., 2021).

Atherosclerosis

11C- and 18F-labelled choline uptake is increased in activated macrophages. Animal models have shown potential usefulness in imaging atherosclerosis (Matter et al., 2006; Laitinen et al., 2010; Hellberg et al., 2016).

Rheumatoid arthritis

[11C]Choline has been shown to accumulate in clinically active synovitis in rheumatoid arthritis. The uptake (measured as SUV and net influx rate, Ki) correlated with the volume of synovium (Roivainen et al., 2003). Initial uptake of [11C]choline is very fast, and the concentration of C-11 label reaches a plateau 10 min after bolus injection (Roivainen et al., 2003; Roivainen & Yli-Kerttula, 2006), suggesting irreversible kinetics during the PET study. Patlak plot was linear (Roivainen et al., 2003), confirming the irreversible uptake. Furthermore, Patlak plot intercept with y axis was close to zero (Roivainen et al., 2003), suggesting that calculation of Patlak plot (requiring dynamic PET scanning) could quantitatively be replaced by FUR, which only requires one late PET scan and enables whole-body imaging.


See also:


Literature

Breeuwsma AJ, Pruim J, Jongen MM, Suurmeijer AJ, Vaalburg W, Nijman RJ, de Jong IJ. In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer. Eur J Nucl Med Mol Imaging 2005; 32(6):668-673. doi: 10.1007/s00259-004-1741-4.

Hara T. 11C-Choline and 2-deoxy-2-[18F]fluoro-D-glucose in tumor imaging with positron emission tomography. Mol Imaging Biol. 2002; 4(4): 267-273. PMID: 14537115.

Krohn KA. Evaluation of alternative approaches for imaging cellular growth. Q J Nucl Med. 2001; 45: 174-178. PMID: 11476167.

Roivainen A, Forsback S, Grönroos T, Lehikoinen P, Kähkönen M, Sutinen E, Minn H. Blood metabolism of [methyl-11C]choline; implications for in vivo imaging with positron emission tomography. Eur J Nucl Med. 2000; 27(1): 25-32. doi: 10.1007/pl00006658.

Roivainen A, Parkkola R, Yli-Kerttula T, Lehikoinen P, Viljanen T, Möttönen T, Nuutila P, Minn H. Use of positron emission tomography with methyl-11C-choline and 2-18F-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium. Arthr Rheum. 2003; 48(11): 3077-3084. doi: 10.1002/art.11282.

Roivainen A, Yli-Kerttula T. Whole-body distribution of 11C-choline and uptake in knee synovitis. Eur J Nucl Med Mol Imaging 2006; 33(11): 1372-1373. doi: 10.1007/s00259-006-0184-5.

Sutinen E, Nurmi M, Roivainen A, Varpula M, Tolvanen T, Lehikoinen P, Minn H. Kinetics of [11C]choline uptake in prostate cancer: a PET study. Eur J Nucl Med Mol Imaging 2004; 31(3): 317-324. doi: 10.1007/s00259-003-1377-9.

Tolvanen T, Yli-Kerttula T, Ujula T, Autio A, Lehikoinen P, Minn H, Roivainen A. Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data. Eur J Nucl Med Mol Imaging 2010; 37(5): 874-883. doi: 10.1007/s00259-009-1346-z.

Utriainen M, Komu M, Vuorinen V, Lehikoinen P, Sonninen P, Kurki T, Utriainen T, Roivainen A, Kalimo H, Minn H. Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS. J Neurooncol. 2003; 62(3): 329-338. doi: 10.1023/a:1023342516925.



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Updated at: 2023-01-28
Created at: 2007-12-03
Written by: Vesa Oikonen