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Originally published as JCO Early Release 10.1200/JCO.2008.18.8581 on October 14 2008 © 2008 American Society of Clinical Oncology.
Premedication With Carbidopa Masks Positive Finding of Insulinoma and β-Cell Hyperplasia in [18F]-Dihydroxy-Phenyl-Alanine Positron Emission Tomography
Turku Positron Emission Tomography Centre, Turku University Hospital, Turku, Finland To the Editor: We read with interest the excellent and valuable article by Koopmans and colleagues concerning staging of carcinoid and islet cell tumors with [18F]-dihydroxy-phenyl-alanine (18F-DOPA) and [11C]-5-hydroxy-tryptophan (11C-5-HTP) positron emission tomography/computed tomography (PET-CT).1 They reported that PET-CT using 11C-5-HTP as a tracer is a more sensitive method in the diagnosis of islet cell tumors compared with PET-CT using tracer 18F-DOPA (96% v 80%). However, we would like to raise concerns regarding that study's use of carbidopa pretreatment before 18F-DOPA PET scanning in patients suspected of having islet cell tumor of the pancreas. We and others have recently shown that when studied without carbidopa pretreatment, 18F-DOPA PET is a highly sensitive method for localization of focal β-cell hyperplasia in infants2 and insulinoma and β-cell hyperplasia in adults.3 We are currently carrying out a prospective study to test the effect of carbidopa on pancreatic 18F-DOPA uptake in patients with suspected islet cell tumor. So far, three consecutive patients have undergone 18F-DOPA PET-CT, both with and without premedication, and all have histological confirmation of the disease. Characteristics of the patients, the findings of different imaging methods, and histopathological data are shown in Table 1. In two out of three patients, insulinoma and β-cell hyperplasia were observed in 18F-DOPA PET without carbidopa premedication but were fully masked when decarboxylation was prevented by carbidopa (Fig 1). In one study patient with insulinoma, both PET scans showed the lesions.
The phenomenon behind this might be explained by the metabolites of F-DOPA. Oral premedication with carbidopa, an inhibitor of amino acid decarboxylase, improves the contrast in PET imaging by increasing the concentration and availability of F-DOPA and 3-O-methyl-6-[18F]-fluoro-L-dopa4 and by reducing urinary radioactivity concentration. It has become a standard procedure in visualization of neuroendocrine tumors (NETs).5,6 A few studies have shown that the image quality improves markedly after pretreatment with carbidopa, as a result of equivalent metabolic pathways.6,7 In addition to the 6-fluorodopamine metabolite, F-DOPA is also the origin of many other metabolites such as 3-O-methyl-6-[18F]-fluoro-L-dopa, 6-fluoro-L-3,4-dihydroxyphenylacetic acid, and 6-fluorohomovanillic acid, as well as sulfated conjugates.8 When the amino acid decarboxylase pathway is blocked with carbidopa, the amount of metabolites changes. So far, the accumulation of these metabolites other than 6-fluorodopamine into various types of NETs is largely unknown. In conclusion, prevention of F-DOPA decarboxylation by means of carbidopa premedication totally prohibited accumulation of radioactivity into the disease focus in two out of three patients with histologically proven insulinoma and β-cell hyperplasia. Our report is the first to demonstrate that imaging of islet cell tumors using PET and labeled amino acid precursors differs from imaging of other NETs. Therefore our recommendation is that until larger studies are available, carbidopa should not be given in 18F-DOPA PET imaging when islet cell tumor is suspected. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
NOTES published online ahead of print atwww.jco.org on October 13, 2008 REFERENCES
1. Koopmans KP, Neels OC, Kema IP, et al: Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 26:1489-1495, 2008 2. Otonkoski T, Nanto-Salonen K, Seppanen M, et al: Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA ositron emission omography. Diabetes 55:13-18, 2006[Medline] 3. Kauhanen S, Seppanen M, Minn H, et al: Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a tool to localize an insulinoma or [beta]-cell hyperplasia in adult patients. J Clin Endocrinol Metab 92:1237-1244, 2007 4. Hoffman JM, Melega WP, Hawk TC, et al: The effects of carbidopa administration on 6-[18F]fluoro-L-dopa kinetics in positron emission tomography. J Nucl Med 33:1472-1477, 1992 5. Orlefors H, Sundin A, Lu L, et al: Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging 33:60-65, 2006[CrossRef][Medline] 6. Koopmans KP, de Vries EG, Kema IP, et al: Staging of carcinoid tumours with 18F-DOPA PET: A prospective, diagnostic accuracy study. Lancet Oncol 7:728-734, 2006[CrossRef][Medline] 7. Brown WD, Oakes TR, DeJesus OT, et al: Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment. J Nucl Med 39:1884-1891, 1998 8. Miletich RS, Comi G, Bankiewicz K, et al: 6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys. Brain Res 626:1-13, 1993[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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