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Open Access 01-12-2020 | Positron Emission Tomography | Original research

[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

Authors: Linjing Mu, Stefanie D. Krämer, Geoffrey I. Warnock, Ahmed Haider, Susan Bengs, Giovanni Cartolano, Dominic S. Bräm, Claudia Keller, Roger Schibli, Simon M. Ametamey, Philipp A. Kaufmann, Catherine Gebhard

Published in: EJNMMI Research | Issue 1/2020

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 < 10 nmol/kg of combined mHED and metaraminol. [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.

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Title: [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
Authors: Linjing Mu
Stefanie D. Krämer
Geoffrey I. Warnock
Ahmed Haider
Susan Bengs
Giovanni Cartolano
Dominic S. Bräm
Claudia Keller
Roger Schibli
Simon M. Ametamey
Philipp A. Kaufmann
Catherine Gebhard
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keyword: Positron Emission Tomography
Published in: EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-020-00700-7

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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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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