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European Journal of Nuclear Medicine and Molecular Imaging

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12.05.2020 | Original Article

First-in-human evaluation of [¹¹C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain

verfasst von: Min-Jeong Kim, Jae-Hoon Lee, Fernanda Juarez Anaya, Jinsoo Hong, William Miller, Sanjay Telu, Prachi Singh, Michelle Y. Cortes, Katharine Henry, George L. Tye, Michael P. Frankland, Jose A. Montero Santamaria, Jeih-San Liow, Sami S. Zoghbi, Masahiro Fujita, Victor W. Pike, Robert B. Innis

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 13/2020

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Abstract

Purpose

This study assessed whether the newly developed PET radioligand [¹¹C]PS13, which has shown excellent in vivo selectivity in previous animal studies, could be used to quantify constitutive levels of cyclooxygenase-1 (COX-1) in healthy human brain.

Methods

Brain test-retest scans with concurrent arterial blood samples were obtained in 10 healthy individuals. The one- and unconstrained two-tissue compartment models, as well as the Logan graphical analysis were compared, and test-retest reliability and time-stability of total distribution volume (V_T) were assessed. Correlation analyses were conducted between brain regional V_T and COX-1 transcript levels provided in the Allen Human Brain Atlas.

Results

In the brain, [¹¹C]PS13 showed highest uptake in the hippocampus and occipital cortex. The pericentral cortex also showed relatively higher uptake compared with adjacent neocortices. The two-tissue compartment model showed the best fit in all the brain regions, and the results from the Logan graphical analysis were consistent with those from the two-tissue compartment model. V_T values showed excellent test-retest variability (range 6.0–8.5%) and good reliability (intraclass correlation coefficient range 0.74–0.87). V_T values also showed excellent time-stability in all brain regions, confirming that there was no radiometabolite accumulation and that shorter scans were still able to reliably measure V_T. Significant correlation was observed between V_T and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [¹¹C]PS13 binding reflects actual COX-1 density in the human brain.

Conclusions

These results from the first-in-human evaluation of the ability of [¹¹C]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation.

Clinical trial registration

NCT03324646 at https://clinicaltrials.gov/. Registered October 30, 2017. Retrospectively registered.

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Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56:387–437. https://doi.org/10.1124/pr.56.3.3.CrossRefPubMed

Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci. 2009;30:174–81. https://doi.org/10.1016/j.tips.2009.01.002.CrossRefPubMedPubMedCentral

Zidar N, Odar K, Glavac D, Jerse M, Zupanc T, Stajer D. Cyclooxygenase in normal human tissues--is COX-1 really a constitutive isoform, and COX-2 an inducible isoform? J Cell Mol Med. 2009;13:3753–63. https://doi.org/10.1111/j.1582-4934.2008.00430.x.CrossRefPubMed

Yasojima K, Schwab C, McGeer EG, McGeer PL. Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res. 1999;830:226–36.CrossRef

Depboylu C, Weihe E, Eiden LE. COX1 and COX2 expression in non-neuronal cellular compartments of the rhesus macaque brain during lentiviral infection. Neurobiol Dis. 2011;42:108–15. https://doi.org/10.1016/j.nbd.2011.01.011.CrossRefPubMedPubMedCentral

Singh P, Shrestha S, Cortes-Salva MY, Jenko KJ, Zoghbi SS, Morse CL, et al. 3-Substituted 1,5-diaryl-1 H-1,2,4-triazoles as prospective PET radioligands for imaging brain COX-1 in monkey. Part 1: synthesis and pharmacology. ACS Chem Neurosci. 2018;9:2610–9. https://doi.org/10.1021/acschemneuro.8b00102.CrossRefPubMedPubMedCentral

Shrestha S, Singh P, Cortes-Salva MY, Jenko KJ, Ikawa M, Kim MJ, et al. 3-Substituted 1,5-diaryl-1 H-1,2,4-triazoles as prospective PET radioligands for imaging brain COX-1 in monkey. Part 2: selection and evaluation of [(11)C]PS13 for quantitative imaging. ACS Chem Neurosci. 2018;9:2620–7. https://doi.org/10.1021/acschemneuro.8b00103.CrossRefPubMedPubMedCentral

Kim MJ, Shrestha SS, Cortes M, Singh P, Morse C, Liow JS, et al. Evaluation of two potent and selective PET radioligands to image COX-1 and COX-2 in rhesus monkeys. J Nucl Med. 2018;59:1907–12. https://doi.org/10.2967/jnumed.118.211144.CrossRefPubMedPubMedCentral

Zoghbi SS, Shetty HU, Ichise M, Fujita M, Imaizumi M, Liow JS, et al. PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements. J Nucl Med. 2006;47:520–7.PubMed

10.

Tonietto M, Rizzo G, Veronese M, Fujita M, Zoghbi SS, Zanotti-Fregonara P, et al. Plasma radiometabolite correction in dynamic PET studies: insights on the available modeling approaches. J Cereb Blood Flow Metab. 2016;36:326–39. https://doi.org/10.1177/0271678x15610585.CrossRefPubMed

11.

Abi-Dargham A, Gandelman M, Zoghbi SS, Laruelle M, Baldwin RM, Randall P, et al. Reproducibility of SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil. J Nucl Med. 1995;36:167–75.PubMed

12.

Gandelman MS, Baldwin RM, Zoghbi SS, Zea-Ponce Y, Innis RB. Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: beta-CIT, IBF, and iomazenil. J Pharm Sci. 1994;83:1014–9. https://doi.org/10.1002/jps.2600830718.CrossRefPubMed

13.

Kanegawa N, Collste K, Forsberg A, Schain M, Arakawa R, Jucaite A, et al. In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects. Brain Behav Immun. 2016;54:149–57. https://doi.org/10.1016/j.bbi.2016.01.019.CrossRefPubMed

14.

Hammers A, Allom R, Koepp MJ, Free SL, Myers R, Lemieux L, et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003;19:224–47. https://doi.org/10.1002/hbm.10123.CrossRefPubMedPubMedCentral

15.

Cunningham VJ, Jones T. Spectral analysis of dynamic PET studies. J Cereb Blood Flow Metab. 1993;13:15–23. https://doi.org/10.1038/jcbfm.1993.5.CrossRefPubMed

16.

Kety SS, Schmidt CF. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values. J Clin Invest. 1948;27:476–83. https://doi.org/10.1172/jci101994.CrossRefPubMedPubMedCentral

17.

Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ. A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol. 1984;15:217–27. https://doi.org/10.1002/ana.410150302.CrossRefPubMed

18.

Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. 1990;10:740–7. https://doi.org/10.1038/jcbfm.1990.127.CrossRefPubMed

19.

Glatting G, Kletting P, Reske SN, Hohl K, Ring C. Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test. Med Phys. 2007;34:4285–92. https://doi.org/10.1118/1.2794176.CrossRefPubMed

20.

Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, et al. Kinetic evaluation and test-retest reproducibility of [(11)C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. 2018;38:2041–52. https://doi.org/10.1177/0271678x17724947.CrossRefPubMed

21.

Parsey RV, Slifstein M, Hwang DR, Abi-Dargham A, Simpson N, Mawlawi O, et al. Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tissue input functions. J Cereb Blood Flow Metab. 2000;20:1111–33. https://doi.org/10.1097/00004647-200007000-00011.CrossRefPubMed

22.

Baumgartner R, Joshi A, Feng D, Zanderigo F, Ogden RT. Statistical evaluation of test-retest studies in PET brain imaging. EJNMMI Res. 2018;8:13. https://doi.org/10.1186/s13550-018-0366-8.CrossRefPubMedPubMedCentral

23.

Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489:391–9. https://doi.org/10.1038/nature11405.CrossRefPubMedPubMedCentral

24.

Rizzo G, Veronese M, Expert P, Turkheimer FE, Bertoldo A. MENGA: a new comprehensive tool for the integration of neuroimaging data and the Allen Human Brain Transcriptome Atlas. PLoS One. 2016;11:e0148744. https://doi.org/10.1371/journal.pone.0148744.CrossRefPubMedPubMedCentral

25.

Arnatkevic Iute A, Fulcher BD, Fornito A. A practical guide to linking brain-wide gene expression and neuroimaging data. Neuroimage. 2019;189:353–67. https://doi.org/10.1016/j.neuroimage.2019.01.011.CrossRef

26.

Jaksik R, Iwanaszko M, Rzeszowska-Wolny J, Kimmel M. Microarray experiments and factors which affect their reliability. Biol Direct. 2015;10:46. https://doi.org/10.1186/s13062-015-0077-2.CrossRefPubMedPubMedCentral

27.

Liu H, Bebu I, Li X. Microarray probes and probe sets. Front Biosci (Elite Ed). 2010;2:325–38. https://doi.org/10.2741/e93.CrossRef

28.

Yermakova AV, Rollins J, Callahan LM, Rogers J, O'Banion MK. Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol. 1999;58:1135–46.CrossRef

29.

Breder CD, Smith WL, Raz A, Masferrer J, Seibert K, Needleman P, et al. Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain. J Comp Neurol. 1992;322:409–38. https://doi.org/10.1002/cne.903220309.CrossRefPubMed

30.

Michell-Robinson MA, Touil H, Healy LM, Owen DR, Durafourt BA, Bar-Or A, et al. Roles of microglia in brain development, tissue maintenance and repair. Brain. 2015;138:1138–59. https://doi.org/10.1093/brain/awv066.CrossRefPubMedPubMedCentral

31.

Hoozemans JJ, Rozemuller AJ, Janssen I, De Groot CJ, Veerhuis R, Eikelenboom P. Cyclooxygenase expression in microglia and neurons in Alzheimer’s disease and control brain. Acta Neuropathol. 2001;101:2–8.CrossRef

Titel: First-in-human evaluation of [11C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain
verfasst von: Min-Jeong Kim
Jae-Hoon Lee
Fernanda Juarez Anaya
Jinsoo Hong
William Miller
Sanjay Telu
Prachi Singh
Michelle Y. Cortes
Katharine Henry
George L. Tye
Michael P. Frankland
Jose A. Montero Santamaria
Jeih-San Liow
Sami S. Zoghbi
Masahiro Fujita
Victor W. Pike
Robert B. Innis
Publikationsdatum: 12.05.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 13/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-04855-2

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

First-in-human evaluation of [¹¹C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain

Abstract

Purpose

Methods

Results

Conclusions

Clinical trial registration

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Clinical trial registration

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