TY - JOUR
T1 - In vivo vesicular acetylcholine transporter density in human peripheral organs: an [
18F]FEOBV PET/CT study.
AU - Horsager, Jacob
AU - Okkels, Niels
AU - Van Den Berge, Nathalie
AU - Jacobsen, Jan
AU - Schact, Anna
AU - Munk, Ole Lajord
AU - Vang, Kim
AU - Bender, Dirk
AU - Brooks, David J
AU - Borghammer, Per
N1 - © 2022. The Author(s).
PY - 2022/4/1
Y1 - 2022/4/1
N2 - BACKGROUND: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [
18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53-86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands.
RESULTS: A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs.CONCLUSION: High [
18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [
18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1 .
AB - BACKGROUND: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [
18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53-86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands.
RESULTS: A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs.CONCLUSION: High [
18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [
18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1 .
KW - Cholinergic neurons
KW - PET imaging
KW - Parasympathetic nervous system
KW - VAChT
KW - Vesicular acetylcholine transporter
KW - [18F]FEOBV
UR - http://www.scopus.com/inward/record.url?scp=85127490850&partnerID=8YFLogxK
U2 - 10.1186/s13550-022-00889-9
DO - 10.1186/s13550-022-00889-9
M3 - Journal article
C2 - 35362761
SN - 2191-219X
VL - 12
JO - EJNMMI research
JF - EJNMMI research
IS - 1
M1 - 17
ER -