Background

[PubMed]

Choline is an important component of phospholipids in the cell membranes. Tissues with increased metabolism will lead to an increased uptake of choline. Choline is phosphorylated by choline kinases (CHK) to phosphorylcholine within cells, and, after several biosynthetic processes, finally is integrated into phospholipids (1). Because tumor cells have a high metabolic rate, choline uptake is high in order to keep up with the demands with the synthesis of phospholipids in their cellular membranes (2). Positron emission tomography (PET) with [¹¹C]Choline has been reported to be useful for the detection and differential diagnosis of brain tumors, prostate cancer, lung cancer, and esophageal cancer (3, 4), whereas [¹⁸F]2-fluoro-2-deoxyglucose (FDG) lacks of specificity or sensitivity (3).

Synthesis

[PubMed]

[¹¹C]Methylcholine was produced by reacting [¹¹C]methyliodide with 2-dimethylaminoethanol. Purified [¹¹C]choline was produced with a measured specific activity of 11.1 GBq/μmol (>300 mCi/μmol) and a radiochemical purity >98% at 35 min after bombardment. The radiochemical yield for the synthesis and purification was approximately 22% (5). A new method of [¹¹C]choline synthesis was achieved by the reaction of [¹¹C]methyl iodide with dimethylaminoethanol at 120 ºC for 5 min. Purification was performed by evaporation of the reactants, followed by passage of the aqueous solution of the product through a cation-exchange resin cartridge. The total time required for obtaining the finished chemical was 25 min. Radiochemical yield was > 98% with radiochemical purity of > 98%. Chemical purity was > 90% (6). An automated synthesis of [¹¹C]choline with a radiochemical yield of about 42% was reported (7).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Because of the short half-life (20 min) of ¹¹C, [¹⁴C]choline and [³H]choline were often used in in vitro studies. Both [¹⁴C] and [³H]choline were rapidly incorporated into phospholipids into PC-3 human prostate cancer cell line (1) and human astrocytoma cell line (8)

Animal Studies

Human Studies

[PubMed]

A time-course study of a normal 60-year-old man with [¹¹C]choline PET revealed the following organs with high [¹¹C]choline uptake: kidney, liver, pancreas, small intestine content, and salivary gland. Dosimetry of [¹¹C]choline in an ideal man was estimated (3). The total body absorbance dose was 0.00279 mSv/MBq (10.3 mrem/mCi). The kidneys (0.018 mGy/MBq (67 mrad/mCi)) received the highest dose of radioactivity, followed by the liver (0.017 mGy/MBq (63 mrad/mCi)), pancreas (0.013 mGy/MBq (48 mrad/mCi)), and spleen (0.008 mGy/MBq (30 mrad/mCi)). Various tumors of >1600 cancer patients were visualized with both [¹¹C]choline and [¹⁸F]FDG (3). If the tumor was in an organ with high uptake, it was impossible to distinguish the tumor uptake from the normal organ uptake. If the tumor was separated from normal tissue uptake, [¹¹C]choline PET visualized tumors as small as 5 mm in diameter, and FDG PET visualized tumors of 10 mm in diameter. Lung cancer and pulmonary tuberculosis could be differentiated by comparing [¹¹C]choline PET and FDG PET images (11).

[¹¹C]choline PET is a useful tool in diagnosis of brain tumor [PubMed], lung cancer [PubMed], esophageal cancer (12), colorectal cancer (3), bladder cancer (13), and prostate cancer [PubMed].

NIH Support

P50 CA128301, U54 CA119338, R01 CA122602-02

References

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2.

Podo F. Tumour phospholipid metabolism. NMR Biomed. 1999;12(7):413–39. [PubMed: 10654290]

3.

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):267–73. [PubMed: 14537115]

4.

Tian M., Zhang H., Oriuchi N., Higuchi T., Endo K. Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors. Eur J Nucl Med Mol Imaging. 2004;31(8):1064–72. [PubMed: 15014903]

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Rosen M.A., Jones R.M., Yano Y., Budinger T.F. Carbon-11 choline: synthesis, purification, and brain uptake inhibition by 2-dimethylaminoethanol. J Nucl Med. 1985;26(12):1424–8. [PubMed: 3877796]

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Hara T., Kosaka N., Shinoura N., Kondo T. PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med. 1997;38(6):842–7. [PubMed: 9189127]

7.

Hara T., Yuasa M. Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging. Appl Radiat Isot. 1999;50(3):531–3. [PubMed: 10070713]

8.

Narayanan T.K., Said S., Mukherjee J., Christian B., Satter M., Dunigan K., Shi B., Jacobs M., Bernstein T., Padma M., Mantil J. A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma. Mol Imaging Biol. 2002;4(2):147–56. [PubMed: 14537137]

9.

Zheng Q.H., Stone K.L., Mock B.H., Miller K.D., Fei X., Liu X., Wang J.Q., Glick-Wilson B.E., Sledge G.W., Hutchins G.D. [11C]Choline as a potential PET marker for imaging of breast cancer athymic mice. Nucl Med Biol. 2002;29(8):803–7. [PubMed: 12453589]

10.

Friedland R.P., Mathis C.A., Budinger T.F., Moyer B.R., Rosen M. Labeled choline and phosphorylcholine: body distribution and brain autoradiography: concise communication. J Nucl Med. 1983;24(9):812–5. [PubMed: 6604143]

11.

Hara T., Kosaka N., Suzuki T., Kudo K., Niino H. Uptake rates of 18F-fluorodeoxyglucose and 11C-choline in lung cancer and pulmonary tuberculosis: a positron emission tomography study. Chest. 2003;124(3):893–901. [PubMed: 12970014]

12.

Kobori O., Kirihara Y., Kosaka N., Hara T. Positron emission tomography of esophageal carcinoma using (11)C-choline and (18)F-fluorodeoxyglucose: a novel method of preoperative lymph node staging. Cancer. 1999;86(9):1638–48. [PubMed: 10547535]

13.

de Jong I.J., Pruim J., Elsinga P.H., Jongen M.M., Mensink H.J., Vaalburg W. Visualisation of bladder cancer using (11)C-choline PET: first clinical experience. Eur J Nucl Med Mol Imaging. 2002;29(10):1283–8. [PubMed: 12271408]