A comparative study of 18F-ASEM and 18F-DBT-10, two novel PET tracers for the α7 nicotinic acetylcholine receptor, in nonhuman primates


A comparative study of 18F-ASEM and 18F-DBT-10, two novel PET tracers for the α7 nicotinic acetylcholine receptor, in nonhuman primates

Hillmer, A.; Zheng, M.-Q.; Scheunemann, M.; Li, S.; Lin, S.-F.; Labaree, D.; Deuther-Conrad, W.; Carson, R. E.; Brust, P.; Huang, Y.

Introduction:

The α7 subtype of nicotinic acetylcholine receptors (nAChRs) is involved in neuropsychiatric disorders including Alzheimer’s disease, substance abuse, and schizophrenia. Recently, 18F-ASEM and 18F-DBT-10 were developed to image α7 nAChRs in vivo. We performed PET studies in nonhuman primates to directly compare the pharmacokinetic properties of these tracers.
Methods:
18F-ASEM and 18F-DBT-10 were produced via nucleophilic substitution of their respective nitro-precursors. PET data were acquired with a Focus-220 scanner in two rhesus monkeys. Bolus injection of tracer was followed by 240 min of PET acquisition, including arterial plasma assay and metabolite analysis to determine the input function. Blocking studies with cold ASEM were conducted to assess the extent of specific binding. Data were analyzed with the one- and two- tissue compartment models (1TCM & 2TCM) and multilinear analysis to measure distribution volumes (VT).
Results:
Both 18F-ASEM and 18F-DBT-10 were prepared in high specific activity and >99% radiochemical purity. Higher parent fractions of 18F-DBT-10 were found, as well as higher plasma free fraction (18F-ASEM:13±3%; 18F-DBT-10:18±2%). Tissue kinetics were faster for 18F-ASEM. The 2TCM best modeled the PET data for both radiotracers. Regional VT values were slightly higher for 18F-DBT-10, ranging from 32-53 mL/cm3 (18F-ASEM) and 35-58 mL/cm3 (18F-DBT-10) with the rank order of thalamus>frontal cortex>striatum=temporal cortex>hippocampus>occipital cortex>cerebellum. Blocking studies decreased VT values from baseline levels throughout the brain.
Conclusion:
18F-ASEM and 18F-DBT-10 both exhibit suitable properties for PET imaging of α7 nAChRs in nonhuman primates. 18F-ASEM exhibits faster kinetics and has been extended to human use (Wong et al., 2014).

  • Lecture (Conference)
    SNMMI 2015, 06.-10.06.2015, Baltimore, Maryland, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Nuclear Medicine 56(2015)3, 33

Permalink: https://www.hzdr.de/publications/Publ-21859
Publ.-Id: 21859