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[$^{11}$C]mHED PET follows a two-tissue compartment model in mouse myocardium with norepinephrine transporter (NET)-dependent uptake, while [$^{18}$F]LMI1195 uptake is NET-independent


Mu, Linjing; Krämer, Stefanie D; Warnock, Geoffrey I; Haider, Ahmed; Bengs, Susan; Cartolano, Giovanni; Bräm, Dominic S; Keller, Claudia; Schibli, Roger; Ametamey, Simon M; Kaufmann, Philipp A; Gebhard, Catherine (2020). [$^{11}$C]mHED PET follows a two-tissue compartment model in mouse myocardium with norepinephrine transporter (NET)-dependent uptake, while [$^{18}$F]LMI1195 uptake is NET-independent. EJNMMI Research, 10(1):114.

Abstract

PURPOSE

Clinical positron emission tomography (PET) imaging of the presynaptic norepinephrine transporter (NET) function provides valuable diagnostic information on sympathetic outflow and neuronal status. As data on the NET-targeting PET tracers [$^{11}$C]meta-hydroxyephedrine ([$^{11}$C]mHED) and [$^{18}$F]LMI1195 ([$^{18}$F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pattern and investigated [$^{11}$C]mHED uptake by kinetic modelling.

METHODS

[$^{11}$C]mHED and [$^{18}$F]LMI1195 accumulation in the heart was studied by PET/CT in FVB/N mice. To test for specific uptake by NET, desipramine, a selective NET inhibitor, was administered by intraperitoneal injection. [$^{11}$C]mHED kinetic modelling with input function from an arteriovenous shunt was performed in three mice.

RESULTS

Both tracers accumulated in the mouse myocardium; however, only [$^{11}$C]mHED uptake was significantly reduced by excess amount of desipramine. Myocardial [$^{11}$C]mHED uptake was half-saturated at 88.3 nmol/kg of combined mHED and metaraminol residual. After [$^{11}$C]mHED injection, a radiometabolite was detected in plasma and urine, but not in the myocardium. [$^{11}$C]mHED kinetics followed serial two-tissue compartment models with desipramine-sensitive K$_{1}$.

CONCLUSION

PET with [$^{11}$C]mHED but not [$^{18}$F]LMI1195 provides information on NET function in the mouse heart. [$^{11}$C]mHED PET is dose-independent in the mouse myocardium at < 10 nmol/kg of combined mHED and metaraminol. [$^{11}$C]mHED kinetics followed serial two-tissue compartment models with K$_{1}$ representing NET transport. Myocardial [$^{11}$C]mHED uptake obtained from PET images may be used to assess cardiac sympathetic integrity in mouse models of cardiovascular disease.

Abstract

PURPOSE

Clinical positron emission tomography (PET) imaging of the presynaptic norepinephrine transporter (NET) function provides valuable diagnostic information on sympathetic outflow and neuronal status. As data on the NET-targeting PET tracers [$^{11}$C]meta-hydroxyephedrine ([$^{11}$C]mHED) and [$^{18}$F]LMI1195 ([$^{18}$F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pattern and investigated [$^{11}$C]mHED uptake by kinetic modelling.

METHODS

[$^{11}$C]mHED and [$^{18}$F]LMI1195 accumulation in the heart was studied by PET/CT in FVB/N mice. To test for specific uptake by NET, desipramine, a selective NET inhibitor, was administered by intraperitoneal injection. [$^{11}$C]mHED kinetic modelling with input function from an arteriovenous shunt was performed in three mice.

RESULTS

Both tracers accumulated in the mouse myocardium; however, only [$^{11}$C]mHED uptake was significantly reduced by excess amount of desipramine. Myocardial [$^{11}$C]mHED uptake was half-saturated at 88.3 nmol/kg of combined mHED and metaraminol residual. After [$^{11}$C]mHED injection, a radiometabolite was detected in plasma and urine, but not in the myocardium. [$^{11}$C]mHED kinetics followed serial two-tissue compartment models with desipramine-sensitive K$_{1}$.

CONCLUSION

PET with [$^{11}$C]mHED but not [$^{18}$F]LMI1195 provides information on NET function in the mouse heart. [$^{11}$C]mHED PET is dose-independent in the mouse myocardium at < 10 nmol/kg of combined mHED and metaraminol. [$^{11}$C]mHED kinetics followed serial two-tissue compartment models with K$_{1}$ representing NET transport. Myocardial [$^{11}$C]mHED uptake obtained from PET images may be used to assess cardiac sympathetic integrity in mouse models of cardiovascular disease.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Language:English
Date:29 September 2020
Deposited On:15 Jan 2021 08:59
Last Modified:01 Feb 2021 16:23
Publisher:SpringerOpen
ISSN:2191-219X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13550-020-00700-7
PubMed ID:32990788

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