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Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic PET ligand to image inflammation

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Abstract

Purpose

The positron emission tomography (PET) radiotracer 11C-(R)-PK11195 allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO), previously called peripheral benzodiazepine receptor (PBR), a marker of inflammation. Despite its widespread use, the radiation burden associated with 11C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging with PET and 11C-(R)-PK11195 in healthy humans.

Methods

Five healthy male volunteers were scanned with PET and 11C-(R)-PK11195, using a dynamic whole-body imaging protocol. An organ-specific method was used to measure accumulated radioactivity in source organs, and residence times were calculated as areas under the curve of time-activity curves expressed as percentage of injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0 software to model the equivalent organ doses and the effective dose for the 70-kg man.

Results

After intravenous injection of 11C-(R)-PK11195, radioactivity accumulated in organs rich in TSPO as well as routes of excretion: the hepatobiliary system and the urine. The mean effective dose was 4.8 µSv/MBq according to International Commission on Radiological Protection (ICRP) Publication 60 and 5.1 µSv/MBq according to ICRP Publication 103, and the highest equivalent organ doses were observed in the kidneys (14.0 µSv/MBq), spleen (12.5 µSv/MBq) and small intestine (12.2 µSv/MBq).

Conclusion

Imaging of TSPO with PET using 11C-(R)-PK11195 is associated with modest radiation exposure, similar in magnitude to most other 11C-labelled PET tracers, suggesting feasibility of 11C-(R)-PK11195 imaging in clinical human studies involving multiple scans in the same subjects per year.

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References

  1. Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapère JJ, Lindemann P, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 2006;27:402–9.

    Article  CAS  PubMed  Google Scholar 

  2. Chen M-K, Guilarte TK. Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther 2008;118:1–17.

    Article  CAS  PubMed  Google Scholar 

  3. Cosenza-Nashat M, Zhao ML, Suh HS, Morgan J, Natividad R, Morgello S, et al. Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol 2009;35:306–28.

    Article  CAS  PubMed  Google Scholar 

  4. Charbonneau P, Syrota A, Crouzel C, Valois JM, Prenant C, Crouzel M. Peripheral-type benzodiazepine receptors in the living heart characterized by positron emission tomography. Circulation 1986;73:476–83.

    CAS  PubMed  Google Scholar 

  5. Cagnin A, Kassiou M, Meikle SR, Banati RB. Positron emission tomography imaging of neuroinflammation. Neurotherapeutics 2007;4:443–52.

    Article  CAS  PubMed  Google Scholar 

  6. Venneti S, Lopresti BJ, Wiley CA. The peripheral benzodiazepine receptor (translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol 2006;80:308–22.

    Article  CAS  PubMed  Google Scholar 

  7. Chauveau F, Boutin H, Van Camp N, Dollé F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging 2008;35:2304–19.

    Article  PubMed  Google Scholar 

  8. Roivainen A, Någren K, Hirvonen J, Oikonen V, Virsu P, Tolvanen T, et al. Whole-body distribution and metabolism of [N-methyl-11C](R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinolinecarboxamide in humans; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography. Eur J Nucl Med Mol Imaging 2009;36:671–82.

    Article  CAS  PubMed  Google Scholar 

  9. ICRP Publication 30: Dosimetric model for the gastrointestinal tract. Ann ICRP 1979;2(3–4):30–4.

    Google Scholar 

  10. Stabin MG, Sparks RB, 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  Google Scholar 

  11. ICRP Publication 60: Recommendation of the International Commission on Radiological Protection. Ann ICRP 1991;21:493–502.

    Google Scholar 

  12. ICRP Publication 103: The 2007 Recommendations of the International Commission on Radiological Protection. Ann ICRP 2007;37:1–333.

    Google Scholar 

  13. ICRP Publication 89: Basic anatomical and physiological data for use in radiological protection: reference values. Ann ICRP 2002;32:1–277.

    Google Scholar 

  14. Fujimura Y, Kreisl WC, Zoghbi SS, Hong J, Gladding RL, Pike VW, et al. Quantification of specific binding in brain and radiation dosimetry of [11C](R)-PK 11195 in rhesus monkey. Neuroimage 2008;41:T112.

    Article  Google Scholar 

  15. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001;358:461–7.

    Article  CAS  PubMed  Google Scholar 

  16. Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 2000;123:2321–37.

    Article  PubMed  Google Scholar 

  17. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis 2008;32:412–9.

    Article  CAS  PubMed  Google Scholar 

  18. Shields AF, Graham MM, Kozawa SM, Kozell LB, Link JM, Swenson ER, et al. Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds. J Nucl Med 1992;33:581–4.

    CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    CAS  PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. Scheinin NM, Tolvanen TK, Wilson IA, Arponen EM, Någren KA, Rinne JO. Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. J Nucl Med 2007;48:128–33.

    CAS  PubMed  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    CAS  PubMed  Google Scholar 

  28. Sprague DR, Fujita M, Ryu YH, Liow JS, Pike VW, Innis RB. Whole-body biodistribution and radiation dosimetry in monkeys and humans of the phosphodiesterase 4 radioligand [(11)C](R)-rolipram: comparison of two-dimensional planar, bisected and quadrisected image analyses. Nucl Med Biol 2008;35:493–500.

    Article  CAS  PubMed  Google Scholar 

  29. Seltzer MA, Jahan SA, Sparks R, Stout DB, Satyamurthy N, Dahlbom M, et al. Radiation dose estimates in humans for (11)C-acetate whole-body PET. J Nucl Med 2004;45:1233–6.

    CAS  PubMed  Google Scholar 

  30. Nugent AC, Neumeister A, Drevets WC, Eckelman WC, Channing MA, Herscovitch P. Human biodistribution and dosimetry of the PET benzodiazepine receptor ligand 11C-flumazenil. J Nucl Med 2004;45(Suppl):434P.

    Google Scholar 

  31. Deloar HM, Fujiwara T, Nakamura T, Itoh M, Imai D, Miyake M, et al. Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body positron emission tomography. Eur J Nucl Med 1998;25:629–33.

    Article  CAS  PubMed  Google Scholar 

  32. 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 D1 receptor radioligand 11C-NNC 112 in humans. J Nucl Med 2006;47:100–4.

    CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Slifstein M, Hwang DR, Martinez D, Ekelund J, Huang Y, Hackett E, et al. Biodistribution and radiation dosimetry of the dopamine D2 ligand 11C-raclopride determined from human whole-body PET. J Nucl Med 2006;47:313–9.

    CAS  PubMed  Google Scholar 

  35. Ribeiro MJ, Ricard M, Bourgeois S, Lièvre MA, Bottlaender M, Gervais P, et al. Biodistribution and radiation dosimetry of [11C]raclopride in healthy volunteers. Eur J Nucl Med Mol Imaging 2005;32:952–8.

    Article  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. Marthi K, Hansen SB, Jakobsen S, Bender D, Smith SB, Smith DF. Biodistribution and radiation dosimetry of [N-methyl-11C]mirtazapine, an antidepressant affecting adrenoceptors. Appl Radiat Isot 2003;59:175–9.

    Article  CAS  PubMed  Google Scholar 

  38. Lu JQ, Ichise M, Liow JS, Ghose S, Vines D, Innis RB. Biodistribution and radiation dosimetry of the serotonin transporter ligand 11C-DASB determined from human whole-body PET. J Nucl Med 2004;45:1555–9.

    CAS  PubMed  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Parsey RV, Belanger MJ, Sullivan GM, Simpson NR, Stabin MG, Van Heertum R, et al. Biodistribution and radiation dosimetry of 11C-WAY100,635 in humans. J Nucl Med 2005;46:614–9.

    CAS  PubMed  Google Scholar 

  41. Sprague DR, Chin FT, Liow JS, Fujita M, Burns HD, Hargreaves R, et al. Human biodistribution and radiation dosimetry of the tachykinin NK1 antagonist radioligand [18F]SPA-RQ: comparison of thin-slice, bisected, and 2-dimensional planar image analysis. J Nucl Med 2007;48:100–7.

    CAS  PubMed  Google Scholar 

  42. Fujita M, Imaizumi M, Zoghbi SS, Fujimura Y, Farris AG, Suhara T, et al. Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation. Neuroimage 2008;40:43–52.

    Article  PubMed  Google Scholar 

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Acknowledgements

The skilful assistance of the staff of Turku PET Centre is greatly appreciated.

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Authors and Affiliations

  1. Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland

    Jussi Hirvonen, Anne Roivainen, Jere Virta, Semi Helin, Kjell Någren & Juha O. Rinne

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  1. Jussi Hirvonen
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Correspondence to Juha O. Rinne.

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Hirvonen, J., Roivainen, A., Virta, J. et al. Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic PET ligand to image inflammation. Eur J Nucl Med Mol Imaging 37, 606–612 (2010). https://doi.org/10.1007/s00259-009-1298-3

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  • DOI: https://doi.org/10.1007/s00259-009-1298-3

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