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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 [11C]meta-hydroxyephedrine ([11C]mHED) and [18F]LMI1195 ([18F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pattern and investigated [11C]mHED uptake by kinetic modelling.Methods
[11C]mHED and [18F]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. [11C]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 [11C]mHED uptake was significantly reduced by excess amount of desipramine. Myocardial [11C]mHED uptake was half-saturated at 88.3 nmol/kg of combined mHED and metaraminol residual. After [11C]mHED injection, a radiometabolite was detected in plasma and urine, but not in the myocardium. [11C]mHED kinetics followed serial two-tissue compartment models with desipramine-sensitive K1.Conclusion
PET with [11C]mHED but not [18F]LMI1195 provides information on NET function in the mouse heart. [11C]mHED PET is dose-independent in the mouse myocardium at 11C]mHED kinetics followed serial two-tissue compartment models with K1 representing NET transport. Myocardial [11C]mHED uptake obtained from PET images may be used to assess cardiac sympathetic integrity in mouse models of cardiovascular disease.
SUBMITTER: Mu L
PROVIDER: S-EPMC7524946 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Mu Linjing L Krämer Stefanie D SD Warnock Geoffrey I GI Haider Achi A Bengs Susan S Cartolano Giovanni G Bräm Dominic S DS Keller Claudia C Schibli Roger R Ametamey Simon M SM Kaufmann Philipp A PA Gebhard Catherine C
EJNMMI research 20200929 1
<h4>Purpose</h4>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 [<sup>11</sup>C]meta-hydroxyephedrine ([<sup>11</sup>C]mHED) and [<sup>18</sup>F]LMI1195 ([<sup>18</sup>F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pa ...[more]