Several
therapeutics and
biomarkers that target
Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six
radiopharmaceuticals to image patients with AD and related
dementias, specifically [11C]UCB-J and [18F]SynVesT-1 for synaptic vesicle
glycoprotein 2A as a marker of synaptic density, two
vesicular acetylcholine transporter PET radiotracers: [18F]FEOBV and [18F]VAT, as well as the transmembrane
AMPA receptor regulatory
protein (TARP)-γ8 tracer, [18F]JNJ-64511070, and the
muscarinic acetylcholine receptor (mAChR) M4 tracer [11C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with
tritium or 18F) by measuring their density variability in pathologically diagnosed cases of AD,
mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section in vitro autoradiography (ARG). Region of interest analysis was used to quantify radioligand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [3H]UCB-J, [3H]SynVesT-1, [3H]JNJ-64511070, and [3H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related
dementias.