Abstract
BackgroundThe objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (−)-(1-((2R,3R)-8-(2-[18F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([18F]VAT) based on PET imaging in nonhuman primates. [18F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia.MethodsThree macaque fascicularis (two males, one female) received 185.4–198.3 MBq [18F]VAT prior to whole-body imaging in a MicroPET-F220 scanner. Time activity curves (TACs) were created from regions of interest (ROIs) that encompassed the entire small organs or samples with the highest activity within large organs. Organ residence times were calculated based on the TACs. We then used OLINDA/EXM 1.1 to calculate human radiation dose estimates based on scaled organ residence times.ResultsMeasurements from directly sampled arterial blood yielded a residence time of 0.30 h in agreement with the residence time of 0.39 h calculated from a PET-generated time activity curve measured in the left ventricle. Organ dosimetry revealed the liver as the critical organ (51.1 and 65.4 μGy/MBq) and an effective dose of 16 and 19 μSv/MBq for male and female, respectively.ConclusionsThe macaque biodistribution data showed high retention of [18F]VAT in the liver consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [18F]VAT can be administered to obtain imaging in humans.
Highlights
The objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (−)-(1-((2R,3R)-8-(2-[18F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin4-yl)(4-fluorophenyl)-methanone ([18F]VAT) based on PET imaging in nonhuman primates. [18F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia
Alterations in cholinergic function could contribute to involuntary movements that develop in people with Parkinson’s disease (PD) called L-dopa-induced dyskinesias (LID)
Cholinergic neurons in the pedunculopontine nucleus (PPN) and their thalamic efferent terminals could be involved in postural instability in PD [3]
Summary
The objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (−)-(1-((2R,3R)-8-(2-[18F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin4-yl)(4-fluorophenyl)-methanone ([18F]VAT) based on PET imaging in nonhuman primates. [18F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia. [18F]VAT has potential for investigation of neurological disorders including Alzheimer’s disease, Parkinson’s disease, and dystonia. Striatal cholinergic interneurons modulate the function of dopaminergic and glutamatergic inputs to striatum from other brain regions including the substantia nigra, thalamus, and cortex. Cholinergic projections target other brain regions including the hippocampus, cerebellar vermis, and thalamus. Mounting evidence implicates abnormalities in cholinergic systems in numerous neurological conditions such as Parkinson’s disease (PD), dystonia, and Alzheimer’s disease (AD). Changes in nicotinic acetylcholine receptors may correlate with cognitive dysfunction in PD [4, 5]. The well-known clinical response to anticholinergic medications in dystonia suggests pathologic involvement of cholinergic neurons. The severity of cognitive dysfunction in AD correlates with loss of cholinergic neurons in CNS [7]. The basal forebrain has showed marked loss of cholinergic neurons in AD autopsy studies [8]
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