6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression.
BACKGROUND
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy.


OBJECTIVE
The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings.


METHODS
Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study.


METHODS
Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex, subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein, two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive adrenal incidentalomas.


METHODS
In all patients computed tomography scan and/or magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed. Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine transporter (VMAT)-1 and -2 and other markers.


RESULTS
A total of 64 lesions were found with both functional imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1 expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause.


CONCLUSIONS
FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-scintigraphy.
Fottner
C
C
I. Medical Clinic, Department of Endocrinology and Metabolism, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. fottner@endokrinologie.klinik.uni-mainz.de
Helisch
A
A
Anlauf
M
M
Rossmann
H
H
Musholt
T J
TJ
Kreft
A
A
Schadmand-Fischer
S
S
Bartenstein
P
P
Lackner
K J
KJ
Klöppel
G
G
Schreckenberger
M
M
Weber
M M
MM
D019797:3-Iodobenzylguanidine; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015415:Biomarkers; D003627:Data Interpretation, Statistical; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D010673:Pheochromocytoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
D015415:Biomarkers; D005819:Genetic Markers; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C043437:fluorodopa F 18; D019797:3-Iodobenzylguanidine; D004295:Dihydroxyphenylalanine