[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

EJNMMI Research

Simon M. Ametamey¹  Giovanni Cartolano¹  Dominic S. Bräm¹  Stefanie D. Krämer¹  Claudia Keller¹  Roger Schibli¹  Philipp A. Kaufmann²  Susan Bengs³  Ahmed Haider³  Geoffrey I. Warnock³  Catherine Gebhard³  Linjing Mu⁴ 

[1] Department of Chemistry and Applied Biosciences, Radiopharmaceutical Sciences, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland;Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland;Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland;Center for Molecular Cardiology, University of Zurich, 8952, Schlieren, Switzerland;Department of Nuclear Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland;Department of Chemistry and Applied Biosciences, Radiopharmaceutical Sciences, Institute of Pharmaceutical Sciences, ETH Zurich, 8093, Zurich, Switzerland;

关键词: [C]meta-hydroxyephedrine ([C]mHED);    [F]LMI1195 ([F]flubrobenguane);    Norepinephrine transporter (NET, SLC6A2);    Cardiac sympathetic innervation imaging;    Small animal PET;    Kinetic modelling;   

DOI  :  10.1186/s13550-020-00700-7

来源: Springer

【 摘 要 】

PurposeClinical 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.ResultsBoth 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.ConclusionPET 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.

【 授权许可】

CC BY