Quantification of the purinergic P2X(7) receptor with [C-11]SMW139 improves through correction for brain-penetrating radiometabolites




Brumberg Joachim, Aarnio Richard, Forsberg Anton, Marjamäki Päivi, Kerstens Vera, Moein Mohammad M, Nag Sangram, Wahlroos Saara, Kassiou Michael, Windhorst Albert D, Halldin Christer, Haaparanta-Solin Merja, Fazio Patrik, Oikonen Vesa, Rinne Juha O, Varrone Andrea

PublisherSage Publications

2023

Journal of Cerebral Blood Flow and Metabolism

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

J CEREBR BLOOD F MET

11

0271-678X

1559-7016

DOIhttps://doi.org/10.1177/0271678X221126830

https://journals.sagepub.com/doi/10.1177/0271678X221126830

https://research.utu.fi/converis/portal/detail/Publication/176967702



The membrane-based purinergic 7 receptor (P2X(7)R) is expressed on activated microglia and the target of the radioligand [C-11]SMW139 for in vivo assessment of neuroinflammation. This study investigated the contribution of radiolabelled metabolites which potentially affect its quantification. Ex vivo high-performance liquid chromatography with a radio detector (radioHPLC) was used to evaluate the parent and radiometabolite fractions of [C-11]SMW139 in the brain and plasma of eleven mice. Twelve healthy humans underwent 90-min [C-11]SMW139 brain PET with arterial blood sampling and radiometabolite analysis. The volume of distribution was estimated by using one- and two- tissue compartment (TCM) modeling with single (V-T) and dual (V-Tp) input functions. RadioHPLC showed three major groups of radiometabolite peaks with increasing concentrations in the plasma of all mice and humans. Two radiometabolite peaks were also visible in mice brain homogenates and therefore considered for dual input modeling in humans. 2TCM with single input function provided V-T estimates with a wide range (0.10-10.74) and high coefficient of variation (COV: 159.9%), whereas dual input function model showed a narrow range of V-Tp estimates (0.04-0.24; COV: 33.3%). In conclusion, compartment modeling with correction for brain-penetrant radiometabolites improves the in vivo quantification of [C-11]SMW139 binding to P2X(7)R in the human brain.


Last updated on 2024-26-11 at 12:07