TY - JOUR

T1 - Characterization of the serotonin 2A receptor selective PET tracer (R)-[18F]MH.MZ in the human brain

AU - Kramer, Vasko

AU - Dyssegaard, Agnete

AU - Flores, Jonathan

AU - Soza-Ried, Cristian

AU - Rösch, Frank

AU - Knudsen, Gitte Moos

AU - Amaral, Horacio

AU - Herth, Matthias M.

PY - 2020

Y1 - 2020

N2 - Purpose: The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.

AB - Purpose: The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.

KW - 5-HT receptor

KW - Kinetic modeling

KW - MDL 100907

KW - Positron emission tomography (PET)

KW - [F]MH.MZ

U2 - 10.1007/s00259-019-04527-w

DO - 10.1007/s00259-019-04527-w

M3 - Journal article

C2 - 31606832

AN - SCOPUS:85074607537

VL - 47

SP - 355

EP - 365

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

ER -