[18F]fluoro-para-hydroxyphenethylguanidine ([18F]pHPG): A Novel PET Radiotracer for Imaging of Metastatic Paraganglioma in Humans

1370 Objectives: We present our initial experience of a novel PET radiotracer, [18F]fluoro-para-hydroxyphenethylguanidine ([18F]pHPG), a substrate of the norepinephrine transporter (NET) and the vesicular monoamine transporter type 2 (VMAT2), for imaging of patients with metastatic paraganglioma (n=2 to date). [18F]pHPG has been previously reported to localize in presynaptic sympathetic nerve terminals in organs that have high sympathetic innervation (eg. heart, adrenals) in normal subjects and demonstrates cardiac denervation in heart failure patients. We hypothesize that [18F]pHPG PET will demonstrate clinical utility in the detection and localization of paraganglioma and pheochromocytoma. Methods: For this study, [18F]3F-pHPG was selected over its structural analog [18F]4F-mHPG due to its less conspicuous uptake in bowel. PET imaging was acquired on a Siemens Biograph TruePoint PET/CT camera at 90 min and 180 min following i.v. injection of 315-445 MBq of [18F]pHPG. Clinical assessment, vital signs, EKG, blood and urine safety laboratory tests were obtained before and after imaging. Six venous blood draws for radiometabolite analysis were performed during the first 1 hour after tracer administration. Effective Dose is 10 mSv, with a critical organ dose to the urinary bladder of 81 mSv. We quantified tissue concentrations (kBq/cc) and standardized uptake values (SUV) of [18F]pHPG retention in tumors and normal organs. Results: Patient 1 is a 29 year-old man with SDHB-related abdominal paraganglioma and metastases evident on bone scan. Patient 2 is a 43 year-old woman with a retroperitoneal paraganglioma metastatic to bone. Both patients had surgical removal of primary tumor prior to imaging. In patient 2, a rapid uptake of [18F]pHPG by 90 min after injection with representative measurements of SUVmax in right parotid 35, thyroid 5.4, left ventricle 13.5, right adrenal 7.9, left adrenal 12.4, and SUVmean in blood-pool 0.5 and liver 0.9 was observed. The first patient had similar biodistribution but additional diffuse activity in the pancreas (Figure) and compensatory uptake in the left adrenal. Intense focal [18F]pHPG uptake in multifocal osseous lytic lesions was found in both patients. Patient 1 had focal uptake in the right adrenalectomy bed and patient 2 had focal uptake in the retroperitoneal surgical bed consistent with recurrent disease. There is no readily discernable difference in localization of metastatic lesions between the 90 min and 180 min PET scans, with comparable quality, and an increase in lesion activity concentrations of ~6% between the two time points. Contemporary [68Ga]DOTATATE PET scans were available with overall similar lesion detection rate for patient 1. In patient 2 there is slight better conspicuity of liver foci on the [18F]pHPG PET versus [68Ga]-DOTATATE PET likely due to less background hepatic radiotracer concentration. Representative target metastatic lesions for SUVmax on [18F]pHPG were right sphenoid bone 38.7, L4 vertebra 27.3, liver metastasis 2.8, and retroperitoneal surgical bed 4.1 compared to [68Ga]DOTATATE(24.5, 44.8, not seen, 24.7, respectively). Conclusions: [18F]pHPG PET imaging is a promising imaging modality for staging of metastatic paraganglioma with the advantages of high lesion affinity, whole body co-registered CT and rapid same day imaging. The biodistribution of [18F]pHPG PET is favorable for future development of a therapeutic analogue. Once COVID-19 pandemic research restrictions are lifted we plan to perform comparisons to FDA approved radiotracers[123I]MIBG and [68Ga]DOTA-TATE in the same subjects. Acknowledgements: This work is supported by an Investigator Award from the Neuroendocrine Tumor Research Foundation (NETRF).