EJNMMI Research (Sep 2020)

[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

  • 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

DOI
https://doi.org/10.1186/s13550-020-00700-7
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 12

Abstract

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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 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 < 10 nmol/kg of combined mHED and metaraminol. [11C]mHED kinetics followed serial two-tissue compartment models with K 1 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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