3-[F]Fluoro--hydroxyphenethylguanidine (3-[F]pHPG) PET-A Novel Imaging Modality for Paraganglioma

Overview

Journal J Endocr Soc

Specialty Endocrinology

Date 2024 Apr 15

PMID 38617812

Authors

Tobias Else

Ka Kit Wong

Kirk A Frey

Allen F Brooks

Benjamin L Viglianti

David M Raffel

Affiliations

Soon will be listed here.

Abstract

Context: Functional positron emission tomography (PET) imaging for the characterization of pheochromocytoma and paraganglioma (PCC/PGL) and for detection of metastases in malignant disease, offers valuable clinical insights that can significantly guide patient treatment.

Objective: This work aimed to evaluate a novel PET radiotracer, 3-[F]fluoro--hydroxyphenethylguanidine (3-[F]pHPG), a norepinephrine analogue, for its ability to localize PCC/PGL.

Methods: 3-[F]pHPG PET/CT whole-body scans were performed on 16 patients (8 male:8 female; mean age 47.6 ± 17.6 years; range, 19-74 years) with pathologically confirmed or clinically diagnosed PCC/PGL. After intravenous administration of 304 to 475 MBq (8.2-12.8 mCi) of 3-[F]pHPG, whole-body PET scans were performed at 90 minutes in all patients. 3-[F]pHPG PET was interpreted for abnormal findings consistent with primary tumor or metastasis, and biodistribution in normal organs recorded. Standardized uptake value (SUV) measurements were obtained for target lesions and physiological organ distributions.

Results: 3-[F]pHPG PET showed high radiotracer uptake and trapping in primary tumors, and metastatic tumor lesions that included bone, lymph nodes, and other solid organ sites. Physiological biodistribution was universally present in salivary glands (parotid, submandibular, sublingual), thyroid, heart, liver, adrenals, kidneys, and bladder. Comparison [Ga]DOTATATE PET/CT was available in 10 patients and in all cases showed concordant distribution. Comparison [I]iodobenzylguanidine [I]mIBG planar scintigraphy and SPECT/CT scans were available for 4 patients, with 3-[F]pHPG showing a greater number of metastatic lesions.

Conclusion: We found the kinetic profile of 3-[F]pHPG PET affords high activity retention within benign and metastatic PCC/PGL. Therefore, 3-[F]pHPG PET imaging provides a novel modality for functional imaging and staging of malignant paraganglioma with advantages of high lesion affinity, whole-body coregistered computed tomography, and rapid same-day imaging.

References

Jung Y, Jang K, Gu G, Koeppe R, Sherman P, Quesada C . [F]Fluoro-Hydroxyphenethylguanidines: Efficient Synthesis and Comparison of Two Structural Isomers as Radiotracers of Cardiac Sympathetic Innervation. ACS Chem Neurosci. 2017; 8(7):1530-1542. PMC: 6108090. DOI: 10.1021/acschemneuro.7b00051. View

Bombardieri E, Giammarile F, Aktolun C, Baum R, Bischof Delaloye A, Maffioli L . 131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010; 37(12):2436-46. DOI: 10.1007/s00259-010-1545-7. View

Kiernan C, Solorzano C . Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment. Surg Oncol Clin N Am. 2015; 25(1):119-38. DOI: 10.1016/j.soc.2015.08.006. View

Pinsard M, Mouchet N, Dion L, Bessede T, Bertrand M, Darai E . Anatomic and functional mapping of human uterine innervation. Fertil Steril. 2022; 117(6):1279-1288. DOI: 10.1016/j.fertnstert.2022.02.013. View

Raffel D, Jung Y, Koeppe R, Jang K, Gu G, Scott P . First-in-Human Studies of [F] Fluorohydroxyphenethylguanidines. Circ Cardiovasc Imaging. 2018; 11(12):e007965. PMC: 6424133. DOI: 10.1161/CIRCIMAGING.118.007965. View

Lenders J, Duh Q, Eisenhofer G, Gimenez-Roqueplo A, Grebe S, Murad M . Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(6):1915-42. DOI: 10.1210/jc.2014-1498. View

Ebbehoj A, Stochholm K, Jacobsen S, Trolle C, Jepsen P, Robaczyk M . Incidence and Clinical Presentation of Pheochromocytoma and Sympathetic Paraganglioma: A Population-based Study. J Clin Endocrinol Metab. 2021; 106(5):e2251-e2261. DOI: 10.1210/clinem/dgaa965. View

Wang P, Li T, Cui Y, Zhuang H, Li F, Tong A . 18 F-MFBG PET/CT Is an Effective Alternative of 68 Ga-DOTATATE PET/CT in the Evaluation of Metastatic Pheochromocytoma and Paraganglioma. Clin Nucl Med. 2022; 48(1):43-48. DOI: 10.1097/RLU.0000000000004447. View

Jung Y, Gu G, Raffel D . Improved synthesis of 4-[ F]fluoro-m-hydroxyphenethylguanidine using an iodonium ylide precursor. J Labelled Comp Radiopharm. 2019; 62(12):835-842. DOI: 10.1002/jlcr.3791. View

10.

Wong K, Else T, Viglianti B, Brooks A, Frey K, Raffel D . PET imaging of metastatic paraganglioma using novel 3-[F]fluoro-para-hydroxyphenethylguanidine (3-[F]pHPG) radiotracer. Eur J Nucl Med Mol Imaging. 2022; 49(6):2098-2099. DOI: 10.1007/s00259-021-05639-y. View

11.

Angelousi A, Kassi E, Zografos G, Kaltsas G . Metastatic pheochromocytoma and paraganglioma. Eur J Clin Invest. 2015; 45(9):986-97. DOI: 10.1111/eci.12495. View

12.

Raffel D, Crawford T, Jung Y, Koeppe R, Gu G, Rothley J . Quantifying cardiac sympathetic denervation: first studies of F-fluorohydroxyphenethylguanidines in cardiomyopathy patients. Eur J Nucl Med Mol Imaging. 2021; 49(2):619-631. DOI: 10.1007/s00259-021-05517-7. View

13.

Kong G, Schenberg T, Yates C, Trainer A, Sachithanandan N, Iravani A . The Role of 68Ga-DOTA-Octreotate PET/CT in Follow-Up of SDH-Associated Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2019; 104(11):5091-5099. DOI: 10.1210/jc.2019-00018. View

14.

Sharma P, Dhull V, Arora S, Gupta P, Kumar R, Durgapal P . Diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in pheochromocytoma. Eur J Nucl Med Mol Imaging. 2013; 41(3):494-504. DOI: 10.1007/s00259-013-2598-1. View

15.

Simsek D, Sanli Y, Kuyumcu S, Basaran B, Mudun A . Ga-DOTATATE PET-CT imaging in carotid body paragangliomas. Ann Nucl Med. 2018; 32(4):297-301. DOI: 10.1007/s12149-018-1242-3. View

16.

Han S, Suh C, Woo S, Kim Y, Lee J . Performance of Ga-DOTA-Conjugated Somatostatin Receptor-Targeting Peptide PET in Detection of Pheochromocytoma and Paraganglioma: A Systematic Review and Metaanalysis. J Nucl Med. 2018; 60(3):369-376. DOI: 10.2967/jnumed.118.211706. View

17.

Chang C, Pattison D, Tothill R, Kong G, Akhurst T, Hicks R . (68)Ga-DOTATATE and (18)F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging. 2016; 16(1):22. PMC: 4989291. DOI: 10.1186/s40644-016-0084-2. View

18.

Pandit-Taskar N, Zanzonico P, Staton K, Carrasquillo J, Reidy-Lagunes D, Lyashchenko S . Biodistribution and Dosimetry of F-Meta-Fluorobenzylguanidine: A First-in-Human PET/CT Imaging Study of Patients with Neuroendocrine Malignancies. J Nucl Med. 2017; 59(1):147-153. PMC: 5750519. DOI: 10.2967/jnumed.117.193169. View