Abstract
Purpose
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. The aim of this study was to evaluate their performance in cardiomyopathy patients.
Methods
Eight cardiomyopathy patients were scanned with 18F-4F-MHPG and 18F-3F-PHPG. Also, regional resting perfusion was assessed with 13N-ammonia. 18F-4F-MHPG and 18F-3F-PHPG kinetics were analyzed using the Patlak graphical method to obtain Patlak slopes Kp (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.
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 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. 18F-4F-MHPG exhibited faster liver clearance than 18F-3F-PHPG, reducing spillover from the liver into the inferior wall. 18F-4F-MHPG was also metabolized more consistently in plasma, which may allow application of population-averaged metabolite corrections.
Conclusion
The advantages of 18F-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.
Trial registration: Registered at the ClinicalTrials.gov website (NCT02669563).
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Acknowledgements
We thank Dr. Peter Scott, Brian Hockley, Bradford Henderson, and Charles Schneider in the University of Michigan PET Radiopharmaceutical Production Program for their support in synthesizing the radiotracers. We also thank our clinical research coordinators Eric Puroll, James Pool, Mary Burton, and Tamara Harper for their many contributions.
Funding
This study was funded by a Mid-Stage Award (MTRAC-N019131) from the University of Michigan Fast Forward Medical Innovation (FFMI) Program and through a Services Award (RSA-000169) from the Science Moving Towards Research Translation and Therapy (SMARTT) Program of the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
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The study was approved by the University of Michigan Institutional Review Board (HUM00105110). This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Raffel, D.M., Crawford, T.C., Jung, YW. et al. Quantifying cardiac sympathetic denervation: first studies of 18F-fluorohydroxyphenethylguanidines in cardiomyopathy patients. Eur J Nucl Med Mol Imaging 49, 619–631 (2022). https://doi.org/10.1007/s00259-021-05517-7
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DOI: https://doi.org/10.1007/s00259-021-05517-7