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

J Clin Endocrinol Metab. 2010 Jun;95(6):2800-10. doi: 10.1210/jc.2009-2352. Epub 2010 Apr 6.


Context: 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.

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

Patients: 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.

Main outcome measures: 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.

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • 3-Iodobenzylguanidine*
  • Adolescent
  • Adrenal Gland Neoplasms / diagnostic imaging*
  • Adrenal Gland Neoplasms / genetics
  • Adrenal Gland Neoplasms / metabolism*
  • Adult
  • Aged
  • Biomarkers
  • Data Interpretation, Statistical
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Female
  • Genetic Markers
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Paraganglioma / diagnostic imaging*
  • Paraganglioma / genetics
  • Paraganglioma / metabolism*
  • Pheochromocytoma / diagnostic imaging*
  • Pheochromocytoma / genetics
  • Pheochromocytoma / metabolism*
  • Positron-Emission Tomography
  • Radiopharmaceuticals*
  • Tomography, X-Ray Computed
  • Vesicular Monoamine Transport Proteins / biosynthesis*
  • Vesicular Monoamine Transport Proteins / genetics
  • Young Adult


  • Biomarkers
  • Genetic Markers
  • Radiopharmaceuticals
  • Vesicular Monoamine Transport Proteins
  • fluorodopa F 18
  • 3-Iodobenzylguanidine
  • Dihydroxyphenylalanine