1. [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
- Author
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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, and Catherine Gebhard
- Subjects
[11C]meta-hydroxyephedrine ([11C]mHED) ,[18F]LMI1195 ([18F]flubrobenguane) ,Norepinephrine transporter (NET, SLC6A2) ,Cardiac sympathetic innervation imaging ,Small animal PET ,Kinetic modelling ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
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 K 1. 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
- Published
- 2020
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