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European Journal of Nuclear Medicine and Molecular Imaging

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01.06.2011 | Original Article

In vivo positron emission tomography imaging with [¹¹C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons

verfasst von: Christine DeLorenzo, Matthew S. Milak, Kathleen G. Brennan, J. S. Dileep Kumar, J. John Mann, Ramin V. Parsey

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2011

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Abstract

Purpose

Metabotropic glutamate receptor subtype 5 (mGluR5) dysfunction has been implicated in several disorders. [¹¹C]ABP688, a positron emission tomography (PET) ligand targeting mGluR5, could be a valuable tool in the development of novel therapeutics for these disorders by establishing in vivo drug occupancy. Due to safety concerns in humans, these studies may be performed in nonhuman primates. Therefore, in vivo characterization of [¹¹C]ABP688 in nonhuman primates is essential.

Methods

Test–retest studies were performed in baboons (Papio anubis) to compare modeling approaches and determine the optimal reference region. The mGluR5-specific antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) was then used in test–block studies, in which ligand binding was measured before and after MTEP administration. Test/block data were analyzed both by calculating changes in binding and using a graphical approach, which allowed estimation of both MTEP occupancy and nonspecific binding.

Results

Test–retest results, which have not been previously reported for [¹¹C]ABP688, indicated that [¹¹C]ABP688 variability is low using an unconstrained two-tissue compartment model. The most appropriate, though not ideal, reference region was found to be the gray matter of the cerebellum. Using these optimal modeling techniques on the test/block data, about 90% occupancy was estimated by the graphical approach.

Conclusion

These studies are the first to demonstrate the specificity of [¹¹C]ABP688 for mGluR5 with in vivo PET in nonhuman primates. The results indicate that, in baboons, occupancy of mGluR5 is detectable by in vivo PET, a useful finding for proceeding to human studies, or performing further baboon studies, quantifying the in vivo occupancy of novel therapeutics targeting mGluR5.

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Titel: In vivo positron emission tomography imaging with [11C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons
verfasst von: Christine DeLorenzo
Matthew S. Milak
Kathleen G. Brennan
J. S. Dileep Kumar
J. John Mann
Ramin V. Parsey
Publikationsdatum: 01.06.2011
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2011
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-010-1723-7

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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