Quantifying cardiac sympathetic denervation. First studies of ${}^{18}$F-fluorohydroxyphenethylguanidines in cardiomyopathy patients [translational research]

4-${}^{18}$F-Fluoro-m-hydroxyphenethylguanidine (${}^{18}$F-4F-MHPG) and 3-${}^{18}$F-fluoro-p-hydroxyphenethylguanidine (${}^{18}$F-3F-PHPG) were developed for quantifying regional cardiac sympathetic nerve density using tracer kinetic analysis. The aim of this study was to evaluate their performance in cardiomyopathy patients. Eight cardiomyopathy patients were scanned with ${}^{18}$F-4F-MHPG and ${}^{18}$F-3F-PHPG. Also, regional resting perfusion was assessed with ${}^{13}$N-ammonia. ${}^{18}$F-4F-MHPG and ${}^{18}$F-3F-PHPG kinetics were analyzed using the Patlak graphical method to obtain Patlak slopes K${}_p$ (mL/min/g) as measures of regional nerve density. Patlak slope polar maps were used to evaluate the pattern and extent of cardiac denervation. For comparison, "retention index" (RI) values (mL blood/min/mL tissue) were also calculated and used to assess denervation. Perfusion polar maps were used to estimate the extent of hypoperfusion. Patlak analysis of ${}^{18}$F-4F-MHPG and ${}^{18}$F-3F-PHPG kinetics was successful in all subjects, demonstrating the robustness of this approach in cardiomyopathy patients. Substantial regional denervation was observed in all subjects, ranging from 25 to 74% of the left ventricle. Denervation zones were equal to or larger than the size of corresponding areas of hypoperfusion. The two tracers provided comparable metrics of regional nerve density and the extent of left ventricular denervation. ${}^{18}$F-4F-MHPG exhibited faster liver clearance than ${}^{18}$F-3F-PHPG, reducing spillover from the liver into the inferior wall. ${}^{18}$F-4F-MHPG was also metabolized more consistently in plasma, which may allow application of population-averaged metabolite corrections. The advantages of ${}^{18}$F-4F-MHPG (more rapid liver clearance, more consistent metabolism in plasma) make it the better imaging agent to carry forward into future clinical studies in patients with cardiomyopathy.