Relative Uptake, Metabolism, and β-Receptor Binding of (1R,2S)-4

The objective of the study was to compare relative uptake, metabolism, and β-receptor affinity of the new positron-emitting uptake-1 tracer (1 R ,2 S )-4-18F-fluorometaraminol (4-FM) with those of the SPECT pharmaceutical meta-123I-iodobenzylguanidine (MIBG) in Wistar Kyoto (WKY) rats and spontaneously hypertensive (SHR) rats. Methods: No-carrier-added 4-18F-FM was applied to SHR and WKY rats in vivo and to retrogradely perfused hearts in vitro. Cardiac and extracardiac distribution was assessed, and metabolite formation was determined by thin-layer chromatography. The in vivo experiments were repeated with no-carrier-added 123I-MIBG. By means of autoradiography, the β-receptor affinity of 4-FM was compared with that of MIBG and propranolol (10 μmol/L) through displacement of 125I-iodocyanopindolol (1.5 pmol/L) in slices of heart and spleen. Results: Cardiomyopathic hearts showed heterogeneous 4-18F-FM uptake with gradients up to 3.6 in vivo and in vitro between different regions of the heart. Control hearts showed such gradients in 4-18F-FM uptake only in vitro. 123I-MIBG exhibited a less heterogeneous in vivo distribution in SHR hearts. Extracardiac differences between WKY and SHR were found for uptake of 4-18F-FM in the spleen (63.3% ± 4% vs. 38.8% ± 5.7% of cardiac activity) and for renal uptake of 123I-MIBG (373% ± 27% vs. 81.4% ± 17% of cardiac activity). Metabolites of 4-18F-FM were found only in the liver and those of 123I-MIBG were found in the liver and kidney with a nearly equal relative fraction in both types of animals of about 20%, 60%, and 30%, respectively. 4-FM suppressed cardiac-specific β-receptor binding of 125I-iodocyanopindolol in heart and spleen of both types of animals significantly, whereas MIBG had almost no effect. Conclusion: The more heterogeneous cardiac distribution of 4-18F-FM suggests that it reflects alterations in uptake-1 better than 123I-MIBG in addition to the possibility of quantification and higher spatial resolution by PET compared with SPECT. Altered biotransformation in cardiomyopathic diseases may also impair the evaluation of 123I-MIBG-SPECT data. The β-receptor binding of 4-18F-FM must be further elucidated.

Mechanisms of COVID-19 pathogenesis in diabetes American Journal of Physiology-Heart and Circulatory Physiology

Loss of adipose TET proteins enhances β-adrenergic responses and protects against obesity by epigenetic regulation of β3-AR expression

Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

Full article: Pathogenicity and virulence of West Nile virus revisited eight decades after its first isolation

Structural perspective of class B1 GPCR signaling: Trends in Pharmacological Sciences

Introduction to Lipids and Lipoproteins - Endotext - NCBI Bookshelf

Inositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites

Vitamin D receptor (VDR) action at target cells. Intracellular