First in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1

S Bhatt, NB Nabulsi, S Li, Z Cai… - Journal of Cerebral …, 2020 - journals.sagepub.com
S Bhatt, NB Nabulsi, S Li, Z Cai, D Matuskey, J Bini, S Najafzadeh, M Kapinos, JR Ropchan…
Journal of Cerebral Blood Flow & Metabolism, 2020journals.sagepub.com
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes enzymatic conversion of
cortisone into the stress hormone cortisol. This first-in-human brain imaging study
characterizes the kinetic modeling and test–retest reproducibility of [18F] AS2471907, a
novel PET radiotracer for 11β-HSD1. Eight individuals underwent one 180-min (n= 4) or two
240-min (n= 4)[18F] AS2471907 PET brain scans (12 total) acquired on the high-resolution
research tomograph (HRRT) scanner with arterial blood sampling. Imaging data were …
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes enzymatic conversion of cortisone into the stress hormone cortisol. This first-in-human brain imaging study characterizes the kinetic modeling and test–retest reproducibility of [18F]AS2471907, a novel PET radiotracer for 11β-HSD1. Eight individuals underwent one 180-min (n = 4) or two 240-min (n = 4) [18F]AS2471907 PET brain scans (12 total) acquired on the high-resolution research tomograph (HRRT) scanner with arterial blood sampling. Imaging data were modeled with 1-tissue (1T) and 2-tissue (2T) compartment models and with multilinear analysis (MA1) to estimate [18F]AS2471907 availability (VT). [18F]AS2471907 demonstrated high, heterogeneous uptake throughout the brain. Of the compartment models, 2T best described [18F]AS2471907 data. Estimates of VT were highly correlated between 2T and MA1 (t* = 30 min) with MA1 yielding VT values ranging from 3.2 ± 1.0 mL/cm3 in the caudate to 15.7 ± 4.2 mL/cm3 in the occipital cortex. The median absolute test–retest variability of 16 ± 5% and high intraclass correlation coefficient (ICC) values of 0.67–0.97 across regions indicate fair test–retest reliability but large intersubject variability. VT estimates using 180 min were within 10% of estimates using full acquisition time. In summary, [18F]AS2471907 exhibits reasonable kinetic properties for imaging 11β-HSD1 in human brain.
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