Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

  • Markus Luster
  • Wolfram Karges
  • Katrin Zeich
  • Sandra Pauls
  • Frederik A. Verburg
  • Henning Dralle
  • Gerhard Glatting
  • Andreas K. Buck
  • Christoph Solbach
  • Bernd Neumaier
  • Sven N. Reske
  • Felix M. Mottaghy
Original Article

Abstract

Purpose

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18F-fluorodihydroxyphenylalanine (18F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone.

Methods

18F-DOPA PET, CT and 18F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology.

Results

Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value.

Conclusion

18F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18F-DOPA PET or CT alone.

Keywords

Pheochromocytoma Multiple endocrine neoplasia type 2 (MEN2) 18F-fluorodihydroxyphenylalanine (18F-DOPA) Positron emission tomography (PET) Computed tomography (CT) Staging 

References

  1. 1.
    Bryant J, Farmer J, Kessler LJ, Townsend RR, Nathanson KL. Pheochromocytoma: the expanding genetic differential diagnosis. J Natl Cancer Inst. 2003;95:1196–204.PubMedCrossRefGoogle Scholar
  2. 2.
    Ilias I, Pacak K. Diagnosis and management of tumors of the adrenal medulla. Horm Metab Res. 2005;37:717–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25:458–511.CrossRefPubMedGoogle Scholar
  4. 4.
    Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006;36:228–47.CrossRefPubMedGoogle Scholar
  5. 5.
    Shapiro B, Gross MD, Shulkin B. Radioisotope diagnosis and therapy of malignant pheochromocytoma. Trends Endocrinol Metab. 2001;12:469–75.CrossRefPubMedGoogle Scholar
  6. 6.
    Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH. Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med. 1985;26:576–85.PubMedGoogle Scholar
  7. 7.
    Troncone L, Rufini V, Danza FM, Donfrancesco A, De Laurentis C, Cozza R, et al. Radioiodinated metaiodobenzylguanidine (*I-MIBG) scintigraphy in neuroblastoma: a review of 160 studies. J Nucl Med Allied Sci. 1990;34:279–88.PubMedGoogle Scholar
  8. 8.
    Sisson JC, Shulkin BL. Nuclear medicine imaging of pheochromocytoma and neuroblastoma. Q J Nucl Med. 1999;43:217–23.PubMedGoogle Scholar
  9. 9.
    Sundin A, Eriksson B, Bergström M, Bjurling P, Lindner KJ, Oberg K, et al. Demonstration of [11C]5-hydroxy-L-tryptophan uptake and decarboxylation in carcinoid tumors by specific positioning labeling in positron emission tomography. Nucl Med Biol. 2000;27:33–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Garnett S, Firnau G, Nahmias C, Chirakal R. Striatal dopamine metabolism in living monkeys examined by positron emission tomography. Brain Res. 1983;280:169–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Reibring L, Agren H, Hartvig P, Tedroff J, Lundqvist H, Bjurling P, et al. Uptake and utilization of [beta-11C]5-hydroxytryptophan in human brain studied by positron emission tomography. Psychiatry Res. 1992;45:215–25.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoegerle S, Altehoefer C, Ghanem N, Brink I, Moser E, Nitzsche E. 18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. Eur J Nucl Med. 2001;28:64–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Hoegerle S, Nitzsche E, Altehoefer C, Ghanem N, Manz T, Brink I, et al. Pheochromocytomas: detection with 18F DOPA whole body PET—initial results. Radiology. 2002;222:507–12.CrossRefPubMedGoogle Scholar
  14. 14.
    de Vries EFJ, Luurtsema G, Brüssermann M, Elsinga PH, Vaalburg W. Fully automated synthesis module for the high yield one-pot preparation of 6-[18F]fluoro-L-DOPA. Appl Radiat Isot. 1999;51:389–94.CrossRefGoogle Scholar
  15. 15.
    Orlefors G, Sundin A, Lu L, Oberg K, Långström B, Eriksson B, 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. 2006;33:60–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Timmers HJ, Hadi M, Carrasquillo JA, Chen CC, Martiniova L, Whatley M, et al. The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. J Nucl Med. 2007;48:1599–606.CrossRefPubMedGoogle Scholar
  17. 17.
    Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med. 2000;41:1369–79.PubMedGoogle Scholar
  18. 18.
    Beheshti M, Pöcher S, Vali R, Waldenberger P, Broinger G, Nader M, et al. The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Eur Radiol. 2009;19:1425–34.CrossRefPubMedGoogle Scholar
  19. 19.
    Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H, et al. Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology. 2001;220:373–80.PubMedGoogle Scholar
  20. 20.
    Imani F, Agopian VG, Auerbach MS, Walter MA, Imani F, Benz MR, et al. 18F-FDOPA PET and PET/CT accurately localize pheochromocytomas. J Nucl Med. 2009;50:513–19.CrossRefPubMedGoogle Scholar
  21. 21.
    Fiebrich HB, Brouwers A, Kerstens MN, Pijl ME, Kema IP, de Jong JR, et al. 6-[F-18]Fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to conventional imaging with (123)I-metaiodobezylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess. J Clin Endocrinol Metab. 2009;94:3922–30. doi:10.210/jc.2009-1054.CrossRefPubMedGoogle Scholar
  22. 22.
    Pacak K, Eisenhofer G, Carrasquillo JA, Chen CC, Li ST, Goldstein DS. 6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma. Hypertension. 2001;38:6–8.PubMedGoogle Scholar
  23. 23.
    Timmers HJ, Hadi M, Carrasquillo JA, Chen CC, Martiniova L, Whatley M, et al. Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-18F-fluorodopamine PET. J Nucl Med. 2007;48:1940–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Timmers HJ, Eisenhofer G, Carrasquillo J, Chen CC, Whatley M, Ling A, et al. Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and metastatic phaeochromocytoma (PHEO). Clin Endocrinol (Oxf). 2009;71:11–7.CrossRefGoogle Scholar
  25. 25.
    Taïeb D, Sebag F, Barlier A, Tessonnier L, Palazzo FF, Morange I, et al. 18F-FDG avidity of pheochromocytomas and parangangliomas: a new molecular imaging signature? J Nucl Med. 2009;50:711–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Taïeb D, Tessonnier L, Sebag F, Niccoli-Sire P, Morange I, Colavolpe C, et al. The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas. Clin Endocrinol (Oxf). 2008;69:580–6.CrossRefGoogle Scholar
  27. 27.
    Shulkin BL, Thompson NW, Shapiro B, Francis IR, Sisson JC. Pheochromocytomas: imaging with 2[fluorine-18]fluoro-2-deoxy-D-glucose PET. Radiology. 1999;212:35–41.PubMedGoogle Scholar
  28. 28.
    Shulkin BL, Wieland DM, Schwaiger M, Thompson NW, Francis IR, Haka MS, et al. PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma. J Nucl Med. 1992;33:1125–31.PubMedGoogle Scholar
  29. 29.
    Trampal C, Engler H, Juhlin C, Bergström M, Långström B. Pheochromocytomas: detection with 11C hydroxyephedrine PET. Radiology. 2004;230:423–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Mann GN, Link JM, Pham P, Picket CA, Byrd DR, Kinahan PE, et al. [11C]metahydroxyephedrine and [18F]fluorodeoxyglucose positron emission tomography improve clinical decision making in suspected pheochromocytoma. Ann Surg Oncol. 2006;13:187–97.CrossRefPubMedGoogle Scholar
  31. 31.
    Win Z, Al-Nahhas A, Towey D, Todd JF, Rubello D, Lewington V, et al. 68Ga-DOTATATE PET in neuroectodermal tumours: first experience. Nucl Med Commun. 2009;28:359–63.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Markus Luster
    • 1
  • Wolfram Karges
    • 2
  • Katrin Zeich
    • 1
  • Sandra Pauls
    • 3
  • Frederik A. Verburg
    • 4
  • Henning Dralle
    • 5
  • Gerhard Glatting
    • 1
  • Andreas K. Buck
    • 1
  • Christoph Solbach
    • 1
  • Bernd Neumaier
    • 1
    • 6
  • Sven N. Reske
    • 1
  • Felix M. Mottaghy
    • 1
    • 7
  1. 1.Department of Nuclear MedicineUniversity of UlmUlmGermany
  2. 2.Division of Endocrinology and DiabetesRWTH AachenAachenGermany
  3. 3.Department of RadiologyUniversity of UlmUlmGermany
  4. 4.Department of Nuclear MedicineUniversity of WürzburgWürzburgGermany
  5. 5.Department of General, Visceral and Vascular SurgeryUniversity Halle-WittenbergHalleGermany
  6. 6.Section for RadiochemistryMax-Planck-Institut für neurologische ForschungCologneGermany
  7. 7.Department of Nuclear MedicineRWTH AachenAachenGermany

Personalised recommendations