Dataset Information

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

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

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

Mu Linjing L Krämer Stefanie D SD Warnock Geoffrey I GI Haider Ahmed 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 [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 pa ...[more]

PMID: 32990788

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