6-l-¹⁸F-Fluorodihydroxyphenylalanine PET in Neuroendocrine Tumors: Basic Aspects and Emerging Clinical Applications

Abstract

In recent years, 6-L-18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the uptake of metabolic precursors, which leads to the uptake of 18 F-DOPA. This nonsystematic review first describes basic aspects of 18 F-DOPA imaging, including radiosynthesis, factors involved in tracer uptake, and various aspects of metabolism and imaging. Subsequently, this review provides an overview of current clinical applications in neuroendocrine tumors, including carcinoid tumors, pancreatic islet cell tumors, pheochromocytoma, paraganglioma, medullary thyroid cancer, hyperinsulinism, and various other clinical entities. The application of PET/CT in carcinoid tumors has unsurpassed sensitivity. In medullary thyroid cancer, pheochromocytoma, and hyperinsulinism, results are also excellent and contribute significantly to clinical management. In the remaining conditions, the initial experience with 18 F-DOPA PET indicates that it seems to be less valuable, but further study is required.

Characterization of Neuroblastic Tumors Using 18F-FDOPA PET

“…Although 18 F-FDOPA PET has been used for striatal imaging in parkinsonism since the 1980s, its application to tumor imaging, especially in neuroendocrine tumors, is promising (6,7). For example, in head and neck paragangliomas, 18 F-FDOPA PET has been proven more efficacious than 18 F-fluorodopamine PET, 18 F-FDG PET, 123 I-MIBG scintigraphy, or 111 In-pentetreotide scintigraphy (29).…”

“…By targeting the catecholamine biosynthesis pathway, 6-18 F-fluoro-L-dihydroxyphenylalanine ( 18 F-FDOPA) PET has been used in visualizing neuroendocrine tumors, such as pheochromocytoma, paraganglioma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma (6,7). 18 F-FDOPA resembles natural L-DOPA, which competes with large neutral amino acids in the plasma and is transported into the neurons by various amino acid transporters (8).…”

Imaging of gastroenteropancreatic neuroendocrine tumors

“…Overall, based on a meta-analysis by Jager et al [76] , the radiolabeled DOPA analogues have reported sensitivities in the range of 65%-96% for the detection of individual lesions, with most of the values in the upper half of this range.…”

Three-Step, “One-Pot” Radiosynthesis of 6-Fluoro-3,4-Dihydroxy-l-Phenylalanine by Isotopic Exchange

“…More recently, it was also found that 6-18 F-fluoro-L-DOPA has potential for oncologic diagnosis (3,4), especially in PET studies of neuroendocrine tumors (5).…”