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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 5/2010

01-05-2010 | Original Article

Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data

Authors: Tuula Tolvanen, Timo Yli-Kerttula, Tiina Ujula, Anu Autio, Pertti Lehikoinen, Heikki Minn, Anne Roivainen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2010

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Abstract

Purpose

Methyl-11C-choline ([11C]choline) is a radiopharmaceutical used for oncological PET studies. We investigated the biodistribution and biokinetics of [11C]choline and provide estimates of radiation doses in humans.

Methods

The distribution of [11C]choline was evaluated ex vivo in healthy rats (n=9) by measuring the radioactivity of excised organs, and in vivo in tumour-bearing rats (n=4) by PET. In addition to estimates of human radiation doses extrapolated from rat data, more accurate human radiation doses were calculated on the basis of PET imaging of patients with rheumatoid arthritis (n=6) primarily participating in a synovitis imaging project with [11C]choline. Dynamic data were acquired from the thorax and abdomen after injection of 423±11 MBq (mean±SD) of tracer. Following PET imaging, the radioactivity in voided urine was measured. The experimental human data were used for residence time estimations. Radiation doses were calculated with OLINDA/EXM.

Results

In rats, the radioactivity distributed mainly to the kidneys, lungs, liver and adrenal gland. The effective dose in a human adult of about 70 kg was 0.0044 mSv/MBq, which is equivalent to 2.0 mSv from 460 MBq of [11C]choline PET. The highest absorbed doses in humans were 0.021 mGy/MBq in the kidneys, 0.020 mGy/MBq in the liver and 0.029 mGy/MBq in the pancreas. Only 2.0% of injected radioactivity was excreted in the urine during the 1.5 h after injection.

Conclusion

The absorbed radiation doses after administration of 460 MBq of [11C]choline were low. Except for the pancreas, biodistribution in the rat was in accordance with that in humans, but rat data may underestimate the effective dose, suggesting that clinical measurements are needed for a more detailed estimation. The observed effective doses suggest the feasibility of [11C]choline PET for human studies.
Literature
1.
Zeisel SH. Choline. A nutrient that is involved in the regulation of cell proliferation, cell death, and cell transformation. Adv Exp Med Biol 1996;399:131–41.PubMed
2.
Ramírez de Molina A, Rodríguez-González A, Gutiérrez R, Martínez-Piñeiro L, Sánchez J, Bonilla F, et al. Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 2000;296:580–3.CrossRef
3.
Cornford EM, Braun LD, Oldendorf WH. Carrier mediated blood-brain barrier transport of choline and certain choline analogs. J Neurochem 1978;30:299–308.CrossRefPubMed
4.
Katz-Brull R, Degani H. Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method. Anticancer Res 1996;16:1375–80.PubMed
5.
Utriainen M, Komu M, Vuorinen V, Lehikoinen P, Sonninen P, Kurki T, et al. Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS. J Neurooncol 2003;62:329–38.CrossRefPubMed
6.
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;86:1638–48.CrossRefPubMed
7.
Sutinen E, Nurmi M, Roivainen A, Varpula M, Tolvanen T, Lehikoinen P, et al. Kinetics of [(11)C]choline uptake in prostate cancer: a PET study. Eur J Nucl Med Mol Imaging 2004;31:317–24.CrossRefPubMed
8.
de Jong IJ, Pruim J, Elsinga PH, Jongen MM, Mensink HJ, Vaalburg W. Visualisation of bladder cancer using (11)C-choline PET: first clinical experience. Eur J Nucl Med Mol Imaging 2002;29:1283–8.CrossRefPubMed
9.
Roivainen A, Parkkola R, Yli-Kerttula T, Lehikoinen P, Viljanen T, Möttönen T, et al. Use of positron emission tomography with methyl-11C-choline and 2-18F-fluoro-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium. Arthritis Rheum 2003;48:3077–84.CrossRefPubMed
10.
Roivainen A, Yli-Kerttula T. Whole-body distribution of (11)C-choline and uptake in knee synovitis. Eur J Nucl Med Mol Imaging 2006;33:1372–3.CrossRefPubMed
11.
Hara T. C-11 Choline and 2-deoxy-2[F-18]fluoro-D-glucose in tumor imaging with positron emission tomography. Mol Imaging Biol 2002;4:267–73.CrossRefPubMed
12.
Roivainen A, Forsback S, Grönroos T, Lehikoinen P, Kähkönen M, Sutinen E, et al. Blood metabolism of [methyl-11C]choline; implications for in vivo imaging with positron emission tomography. Eur J Nucl Med 2000;27:25–32.CrossRefPubMed
13.
Lehikoinen PK, Bergman JR, Hällsten UM, Kokkomäki EPJ, Eskola OI, Solin OH. A simple synthesis of [methyl-11C]choline. J Labelled Comp Radiopharm 1999;42:S480–2.
14.
Howell RW, Wessels BW, Lovinger R. The MIRD perspective 1999. J Nucl Med 1999;40:3S–10S.PubMed
15.
Stabin MG, Sparks R, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46:1023–7.PubMed
16.
Snyder WS, Cook MJ, Nasset ES, Karhausen LR, Howells GP, Tipton IH. Report of the Task Group on Reference Man. Oxford, UK: Pergamon Press; 1974. p. 325–7.
17.
International Commission on Radiological Protection. ICRP Publication 30. Limits for intakes of radionuclides by workers – dosimetric model for bone. Ann ICRP 1979;2:35–46.CrossRef
18.
Friedland RP, Mathis CA, Budinger TF, Moyer BR, Rosen M. Labeled choline and phosphorylcholine: body distribution and brain autoradiography: concise communication. J Nucl Med 1983;24:812–5.PubMed
19.
Haubrich DR, Wang PFL, Wedeking PW. Distribution and metabolism of intravenously administered choline[methyl-3-H] and synthesis in vivo of acetylcholine in various tissues of guinea pigs. J Pharmacol Exp Ther 1975;193:246–55.PubMed
20.
DeGrado TR, Reiman RE, Price DT, Wang S, Coleman RE. Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. J Nucl Med 2002;43:92–6.PubMed
21.
International Commission on Radiological Protection. ICRP Publication 106. Radiation doses to patients from radiopharmaceuticals – a third amendment to ICRP Publication 53. Ann ICRP 2008;38:1–198.
22.
Laymon CM, Mason NS, Frankle WG, Carney JP, Lopresti BJ, Litschge MY, et al. Human biodistribution and dosimetry of the D2/3 agonist 11C-N-propylnorapomorphine (11C-NPA) determined from PET. J Nucl Med 2009;50:814–7.CrossRefPubMed
23.
Treyer V, Streffer J, Ametamey SM, Bettio A, Bläuenstein P, Schmidt M, et al. Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers. Eur J Nucl Med Mol Imaging 2008;35:766–70.CrossRefPubMed
24.
Virta JR, Tolvanen T, Någren K, Brück A, Roivainen A, Rinne JO. 1-11C-methyl-4-piperidinyl-N-butyrate radiation dosimetry in humans by dynamic organ-specific evaluation. J Nucl Med 2008;49:347–53.CrossRefPubMed
25.
Graham MM, Peterson LM, Muzi M, Graham BB, Spence AM, Link JM, et al. 1-[Carbon-11]-glucose radiation dosimetry and distribution in human imaging studies. J Nucl Med 1998;39:1805–10.PubMed
26.
Thees S, Neumaier B, Glatting G, Deisenhofer S, von Arnim CA, Reske SN, et al. Radiation dosimetry and biodistribution of the beta-amyloid plaque imaging tracer 11C-BTA-1 in humans. Nuklearmedizin 2007;46:175–80.PubMed
27.
Scheinin NM, Tolvanen TK, Wilson IA, Arponen EM, Någren KÅ, Rinne JO. Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. J Nucl Med 2007;48:128–33.PubMed
28.
O’Keefe GJ, Saunder TH, Ng S, Ackerman U, Tochon-Danguy HJ, Chan JG, et al. Radiation dosimetry of beta-amyloid tracers 11C-PiB and 18F-BAY94-9172. J Nucl Med 2009;50:309–15.CrossRefPubMed
29.
Liu N, Li M, Li X, Meng X, Yang G, Zhao S, et al. PET-based biodistribution and radiation dosimetry of epidermal growth factor receptor-selective tracer 11C-PD153035 in humans. J Nucl Med 2009;50:303–8.CrossRefPubMed
30.
Santens P, De Vos F, Thierens H, Decoo D, Slegers G, Dierckx RA, et al. Biodistribution and dosimetry of carbon-11-methoxyprogabidic acid, a possible ligand for GABA-receptors in the brain. J Nucl Med 1998;39:307–10.PubMed
31.
Seltzer MA, Jahan SA, Sparks R, Stout DB, Satyamurthy N, Dahlbom M, et al. Radiation dose estimates in humans for C-11-acetate whole-body PET. J Nucl Med 2004;45:1233–6.PubMed
32.
Deloar HM, Fujiwara T, Nakamura T, Itoh M, Imai D, Miyake M, et al. Estimation of internal absorbed dose of L-[methyl-C-11]methionine using whole-body positron emission tomography. Eur J Nucl Med 1998;15:629–33.CrossRef
33.
Cropley VL, Fujita M, Musachio JL, Hong J, Ghose S, Sangare J, et al. Whole-body biodistribution and estimation of radiation-absorbed doses of the dopamine D-1 receptor radioligand C-11-NNC 112 in humans. J Nucl Med 2006;47:100–4.PubMed
34.
Ribeiro MJ, Ricard M, Lièvre MA, Bourgeois S, Emond P, Gervais P, et al. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [(11)C]PE2I in healthy volunteers. Nucl Med Biol 2007;34:465–70.CrossRefPubMed
35.
Slifstein M, Hwang DR, Martinez D, Ekelund J, Huang Y, Hackett E, et al. Biodistribution and radiation dosimetry of the dopamine D-2 ligand C-11-raclopride determined from human whole-body PET. J Nucl Med 2006;47:313–19.PubMed
36.
Ribeiro MJ, Ricard M, Bourgeois S, Lièvre MA, Bottlaender M, Gervais P, et al. Biodistribution and radiation dosimetry of [C-11]raclopride in healthy volunteers. Eur J Nucl Med Mol Imaging 2005;32:952–8.CrossRefPubMed
37.
Brown AK, Fujita M, Fujimura Y, Liow JS, Stabin M, Ryu YH, et al. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med 2007;48:2072–9.CrossRefPubMed
38.
Marthi K, Hansen SB, Jakobsen S, Bender D, Smith SB, Smith DF. Biodistribution and radiation dosimetry of [N-rnethyl-C-11]mirtazapine, an antidepressant affecting adrenoceptors. Appl Radiat Isot 2003;59:175–9.CrossRefPubMed
39.
Lu JQ, Ichise M, Liow JS, Ghose S, Vines D, Innis RB. Biodistribution and radiation dosimetry of the serotonin transporter ligand C-11-DASB determined from human whole-body PET. J Nucl Med 2004;45:1555–9.PubMed
40.
Seneca N, Zoghbi SS, Liow JS, Kreisl W, Herscovitch P, Jenko K, et al. Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein. J Nucl Med 2009;50:807–13.CrossRefPubMed
41.
Parsey RV, Belanger MJ, Sullivan GM, Simpson NR, Stabin MG, Van Heertum R, et al. Biodistribution and radiation dosimetry of C-11-WAY100635 in humans. J Nucl Med 2005;46:614–9.PubMed
42.
International Commission on Radiological Protection. ICRP Publication 80. Recalculated dose data for 19 frequently used radiopharmaceuticals from ICRP Publication 53. Ann ICRP 1998;28:47–83.CrossRef
43.
Parsey RV, Sokol LO, Bélanger MJ, Kumar JS, Simpson NR, Wang T, et al. Amyloid plaque imaging agent [C-11]-6-OH-BTA-1: biodistribution and radiation dosimetry in baboon. Nucl Med Commun 2005;26:875–80.CrossRefPubMed
44.
Harvey J, Firnau G, Garnett ES. Estimation of the radiation dose in man due to 6-[18F]fluoro-L-dopa. J Nucl Med 1985;26:931–5.PubMed
45.
Brown WD, Oakes TR, DeJesus OT, Taylor MD, Roberts AD, Nickles RJ, et al. Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment. J Nucl Med 1998;39:1884–91.PubMed
46.
Tang G, Wang M, Tang X, Luo L, Gan M. Pharmacokinetics and radiation dosimetry estimation of O-(2-[18F]fluoroethyl)-L-tyrosine as oncologic PET tracer. Appl Radiat Isotopes 2003;58:219–25.CrossRef
47.
Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Müller HW, et al. Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine. Eur J Nucl Med Mol Imaging 2003;30:519–24.PubMed
48.
Leggett RW. Reliability of the ICRP’s dose coefficients for members of the public. 1. Sources of uncertainty in the biokinetic models. Radiat Prot Dosimetry 2001;95:199–213.PubMed
Metadata
Title
Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data
Authors
Tuula Tolvanen
Timo Yli-Kerttula
Tiina Ujula
Anu Autio
Pertti Lehikoinen
Heikki Minn
Anne Roivainen
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-009-1346-z

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