Abstract
BackgroundThe melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases. Hence, there is a major interest in in vivo imaging of this receptor. A PET tracer would allow non-invasive in vivo visualization and quantification of the MCHR1. The aim of the study was the ex vivo evaluation of the MCHR1 ligand [18F]FE@SNAP as a potential PET tracer for the MCHR1.Methods[18F]FE@SNAP was injected directly into the jugular vein of awake naïve rats for ex vivo brain autoradiography, biodistribution and additional blood metabolite analysis. Blocking experiments were conducted using the unlabeled MCHR1 ligand SNAP-7941.ResultsA high uptake of [18F]FE@SNAP was observed in the lateral hypothalamus and the ventricular system. Both regions were significantly blocked by SNAP-7941. Biodistribution evinced the highest uptake in the kidneys, adrenals, lung and duodenum. Specific blocking with SNAP-7941 led to a significant tracer reduction in the heart and adrenals. In plasma samples, 47.73 ± 6.1 % of a hydrophilic radioactive metabolite was found 45 min after tracer injection.ConclusionsSince [18F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [18F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the central nervous system. Additionally, this finding is supported by the specific blocking in the ventricular system, where the MCHR1 is expressed in the ependymal cells. These findings suggest that [18F]FE@SNAP could serve as a useful imaging and therapy monitoring tool for MCHR1-related pathologies.
Highlights
The melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases
Besides the application of a MCHR1-positron emission tomography (PET) tracer for compound dose selection of potential MCHR1targeting drugs, another potential implication for Philippe et al EJNMMI Research (2016) 6:31 obesity patients could be the in vivo quantification of the MCHR1—which is predominantly expressed in the lateral hypothalamus [8]—as a risk factor and early diagnostic tool for insulin resistance
We introduced the 18F-fluoroethylated analogue [18F]FE@SNAP (Fig. 1) as an alternative potential PET tracer for the MCHR1 [12, 13]. [18F]FE@SNAP showed a high affinity (Kd = 2.9 nM, evaluated on CHO cells expressing the human MCHR1) and selectivity (Ki > 1000 nM on the second MCH receptor, MCHR2) towards the MCHR1 [13]
Summary
The melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases. The aim of the study was the ex vivo evaluation of the MCHR1 ligand [18F]FE@SNAP as a potential PET tracer for the MCHR1. Conclusions: Since [18F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [18F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the central nervous system. This finding is supported by the specific blocking in the ventricular system, where the MCHR1 is expressed in the ependymal cells.
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