Quantifying Cardiac Sympathetic Denervation: First Studies of 18F-Fluorohydroxyphenethylguanidines in Cardiomyopathy Patients

Abstract Purpose. The PET radiotracers 4-18F-fluoro-m-hydroxyphenethylguanidine (18F-4F-MHPG) and 3-18F-fluoro-p-hydroxyphenethylguanidine (18F-3F-PHPG) were developed for quantifying regional cardiac sympathetic nerve density using tracer kinetic analysis methods. The aim of this study was to evaluate their performance in cardiomyopathy patients.Methods: Eight cardiomyopathy patients selected for surgical placement of an implantable cardioverter defibrillator (ICD) were scanned with 18F-4F-MHPG and 18F-3F-PHPG on different days. In addition, an 13N-ammonia scan was performed to assess regional resting perfusion. The myocardial kinetics of 18F-4F-MHPG and 18F-3F-PHPG were analyzed using the Patlak graphical method to obtain Patlak slopes Kp (mL/min/g) as quantitative metrics of regional nerve density. Polar maps of the Patlak slopes were generated to map regional nerve density and to estimate the extent of cardiac denervation. For comparison purposes, regional tracer 'retention index' (RI) values (mL blood/min/mL tissue) were also calculated and used to estimate denervation extent metrics. Polar maps of resting perfusion estimates were used to estimate the pattern and extent of hypoperfusion.Results: Patlak analysis of 18F-4F-MHPG and 18F-3F-PHPG kinetics was successful in all subjects, demonstrating the robustness of this approach in cardiomyopathy patients. Substantial regional denervation was observed in all eight 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.Conclusion: 18F-4F-MHPG and 18F-3F-PHPG provide quantitative metrics of regional sympathetic nerve density and the extent of left ventricular denervation in patients with cardiomyopathy, supporting further clinical development of these agents.Trial registration: Registered at the ClinicalTrials.gov website (NCT02669563).URL: https://clinicaltrials.gov/ct2/show/NCT02669563