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Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Translocator protein (TSPO) is a promising biomarker for neuroinflammation. We developed two new PET ligands, 18F-PBR06 and 11C-PBR28, to image TSPOs. Although our prior studies suggest that either of the two ligands could be used to quantify TSPOs in human brain, the studies were done in different sets of subjects. In this study, we directly compared 18F-PBR06 and 11C-PBR28 in eight human subjects to determine (1) whether either ligand provides more precise measurements of TSPOs and (2) whether the higher in vitro affinity of PBR06 compared to PBR28 led to higher in vivo binding of 18F-PBR06 compared to 11C-PBR28.

Methods

In vivo binding was calculated as total distribution volume (V T), using an unconstrained two-tissue compartment model. V T was corrected for plasma free fraction (f P) to measure ligand binding based on free ligand concentration in brain.

Results

Both ligands measured V T with similar precision, as evidenced by similarly good identifiability. However, V T for both radioligands increased with increasing lengths of data acquisition, consistent with the accumulation of radiometabolites in brain. Despite its higher lipophilicity and higher in vitro affinity, V T/f P of 18F-PBR06 was similar to that of 11C-PBR28.

Conclusion

Both 18F-PBR06 and 11C-PBR28 are similar in terms of precision, sensitivity to accumulation of radiometabolites, and magnitude of in vivo binding. Thus, selection between the two radioligands will be primarily determined by the logistical impact of the different half-lives of the two radionuclides (110 vs 20 min).

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Notes

  1. Translocator protein was formerly named peripheral benzodiazepine receptor (PBR) because it was originally found as a binding site for diazepam in peripheral organs. To reflect its distribution in both central nervous system and peripheral organs and also to reflect its functions, PBR has been renamed as translocator protein [1].

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Acknowledgements

This research was supported by the Intramural Program of NIMH (project #Z01-MH-002795-07 and #Z01-MH-002793-07). We thank Kacey Anderson, M. Desiree Ferraris Araneta, Robert L. Gladding, Kimberly Jenko, William C. Kreisl, Barbara Scepura, Cheryl Wallisch, and the staff of the PET Department for successful completion of the studies, PMOD Technologies (Zurich, Switzerland) for providing its image analysis and modeling software, and Jussi Hirvonen for assisting statistical analyses.

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Authors and Affiliations

  1. Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B1D43, 10 Center Drive, MSC-1026, Bethesda, MD, 20892-1026, USA

    Leah P. Dickstein, Sami S. Zoghbi, Yota Fujimura, Masao Imaizumi, Yi Zhang, Victor W. Pike, Robert B. Innis & Masahiro Fujita

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  1. Leah P. Dickstein
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  2. Sami S. Zoghbi
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  3. Yota Fujimura
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  4. Masao Imaizumi
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  5. Yi Zhang
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  6. Victor W. Pike
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  7. Robert B. Innis
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  8. Masahiro Fujita
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Correspondence to Masahiro Fujita.

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Dickstein, L.P., Zoghbi, S.S., Fujimura, Y. et al. Comparison of 18F- and 11C-labeled aryloxyanilide analogs to measure translocator protein in human brain using positron emission tomography. Eur J Nucl Med Mol Imaging 38, 352–357 (2011). https://doi.org/10.1007/s00259-010-1622-y

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  • DOI: https://doi.org/10.1007/s00259-010-1622-y

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