Key result
Novel PET tracer 18F-4F-MHPG quantifies cardiac sympathetic nerve density with dose-dependent pharmacological blockade.
Why the study?
A new radiotracer with kinetic properties favorable for quantifying regional cardiac sympathetic nerve density with PET was needed.
[(18)F]4F-MHPG is a promising new PET radiotracer for quantifying regional cardiac sympathetic nerve density, demonstrating favorable kinetics and specific binding in a non-human primate model.
May support preclinical development of sympathetic PET tracers; leaves open clinical translation and human validation.
4-[(18)F]Fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG, [(18)F]1) is a new cardiac sympathetic nerve radiotracer with kinetic properties favorable for quantifying regional nerve density with PET and tracer kinetic analysis. An automated synthesis of [(18)F]1 was developed in which the intermediate 4-[(18)F]fluoro-m-tyramine ([(18)F]16) was prepared using a diaryliodonium salt precursor for nucleophilic aromatic [(18)F]fluorination. In PET imaging studies in rhesus macaque monkeys, [(18)F]1 demonstrated high quality cardiac images with low uptake in lungs and the liver. Compartmental modeling of [(18)F]1 kinetics provided net uptake rate constants Ki (mL/min/g wet), and Patlak graphical analysis of [(18)F]1 kinetics provided Patlak slopes Kp (mL/min/g). In pharmacological blocking studies with the norepinephrine transporter inhibitor desipramine (DMI), each of these quantitative measures declined in a dose-dependent manner with increasing DMI doses. These initial results strongly suggest that [(18)F]1 can provide quantitative measures of regional cardiac sympathetic nerve density in human hearts using PET.
No takes yet. Share an insight, caveat, or question.
Jang et al. (2013) studied Cardiac sympathetic nerve density imaging. 4-[18F]Fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG) vs. Desipramine (pharmacological blocking) was evaluated on Net uptake rate constants (Ki) and Patlak slopes (Kp). PET imaging with [(18)F]4F-MHPG in rhesus macaques provided high-quality cardiac images and quantitative measures of sympathetic nerve density that declined dose-dependently with desipramine.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: