18F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

Abstract

6-Fluoro-(18F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, 123I-metaiodobenzylguanidine (MIBG) and 111In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1–77.6] for FDOPA vs 44 % (95 % CI 35–53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4–97.1) for FDOPA vs 69 % (95 % CI 60.2–77.1) for 123I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3–95.3) for FDOPA vs 80 % (95 % CI 69.2–88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data, could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and 68Ga-labelled peptides.

Zalecenia ogólne dotyczące postępowania w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

“…The 18 FDG -PET/CT examination (fluorodeoxyglucose) is usually negative in well-differentiated NENs, mainly G1 NENs [92,93]. However, it has been demonstrated that collection of 18 FGD in neoplastic foci is a negative prognostic factor [90].…”

In Vivo Biodistribution of No-Carrier-Added 6-18F-Fluoro-3,4-Dihydroxy-l-Phenylalanine (18F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added 18F-DOPA, Prepared by Conventional Electrophilic Substitution

“…This amino acid tracer visualizes those cells that possess the capability to take up the aromatic amino acid precursor and are involved in the biosynthesis of dopamine. 18 F-DOPA has been shown to be a good tracer for welldifferentiated neuroendocrine tumors originating from the gastrointestinal tract (1)(2)(3). In addition, 18 F-DOPA has also been shown to be a good tracer for other types of neuroendocrine tumors, such as neuroblastoma (4), medullary thyroid carcinoma, pheochromocytoma, and paraganglioma (1), and for malignancies of the central nervous system (5).…”

“…18 F-DOPA has been shown to be a good tracer for welldifferentiated neuroendocrine tumors originating from the gastrointestinal tract (1)(2)(3). In addition, 18 F-DOPA has also been shown to be a good tracer for other types of neuroendocrine tumors, such as neuroblastoma (4), medullary thyroid carcinoma, pheochromocytoma, and paraganglioma (1), and for malignancies of the central nervous system (5). Finally, imaging dopamine metabolism in the central nervous system with 18 F-DOPA is an effective means to determine the extent of degeneration of presynaptic dopaminergic neurons in Parkinson disease (6).…”

18F-DOPA and Other Radiopharmaceuticals for Imaging Unknown Primary Neuroendocrine Tumors

“…Therefore, in this clinical scenario, 18 F-DOPA has to be comparable to other radiopharmaceuticals used for imaging NETs, and the choice of the best one depends mainly on the most probable primary neoplasm and its aggressiveness. A recent review on this topic reported that, currently, 18 F-DOPA seems to have better diagnostic accuracy than other radiopharmaceuticals in some precise NET subtypes: medullary thyroid cancer, catecholamine-producing tumors with low aggressiveness, and well-differentiated carcinoid tumors of the midgut, as well as in congenital hyperinsulinism (17). Nevertheless, for correct image interpretation, it is mandatory that the interpreter be well aware of 18 F-DOPA physiologic biodistribution and normal variants, including possible pitfalls that may lead to PET/CT misinterpretations in various clinical settings (18).…”