Journal of Endocrinological Investigation

, Volume 20, Issue 11, pp 648–658 | Cite as

The treatment of malignant pheochromocytoma with Iodine-131 metaiodobenzylguanidine (131I-MIBG): A comprehensive review of 116 reported patients

  • Keh-Chuan Loh
  • P. A. Fitzgerald
  • K. K. Matthay
  • P. P. B. Yeo
  • D. C. Price
Article

Abstract

Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localization of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialized centers around the world. We review our clinical experience together with the published experience of 23 other centers in 10 countries, regarding the use of 131I-MIBG for treating patients with malignant adrenal pheochromocytomas or extra-adrenal paragangliomas. There were a total of 116 evaluable patients: 3 were from our current report and another 113 were reported in the literature from 1983 to 1996. A majority of the patients were selected for treatment based upon positive tracer uptake studies. The cumulative dose of 131I-MIBG administered ranged from 96 to 2,322 mCi (3.6 to 85.9 GBq), with a mean (±SD) of 490±350 mCi (18.1 ±13.0 GBq). The subjects received a mean single therapy dose of 158 mCi (5.8 GBq) and the number of doses administered ranged from 1 to 11, with a mean of 3.3±2.2 doses. Initial symptomatic improvement was achieved in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. Five patients had complete tumor and hormonal responses, ranging from 16 to 58 months, which were sustained at the time of reporting. Patients with metastases to soft tissue had more favorable responses to treatment than those with metastases to bone. No difference was noted in the age between the responders and non-responders. Adverse effects, recorded in 41 % of the treated patients, were generally mild except for one fatality from bone marrow aplasia. Among 89 patients with follow-up data, 45% of the responders had relapsed with recurrent or progressive disease after a mean interval of 29.3±31.1 months (median 19 months). Of patients with an initial response to 131I-MIBG, death was reported in 33% after a mean of 23.2±8.1 months (median 22 months) following treatment. Of non-responders, death was reported in 45% after a mean of 14.3±8.3 months (median 13 months). In conclusion, this review suggests that 131I-MIBG therapy may be a useful palliative adjunct in selected patients with malignant pheochromocytoma or paraganglioma. Although controlled studies are lacking, our review raises the hope that this therapeutic modality may prolong survival with an occasional sustained complete remission or possible cure.

Key-words

Malignant pheochromocytoma paraganglioma radionuclide therapy iodine-131 metaiodobenzylguanidine (131I-MIBG) treatment review 

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References

  1. 1.
    Van Heerden J.A., Sheps S.G., Hamberger B., Sheedy P.F., Poston J.G., Remine W.H. Pheochromocytoma: current status and changing trends. Surgery. 91: 367, 1982.PubMedGoogle Scholar
  2. 2.
    Mahoney E.M., Harrison J.H. Malignant pheochromocytoma: clinical course and treatment. J.Urol. 118: 225, 1977.PubMedGoogle Scholar
  3. 3.
    Drasin H. Treatment of malignant pheochromocytoma. West. J. Med. 128: 106, 1978.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Robinson R.G., DeQuattro V., Grushkin C.M., Lieberman E. Childhood pheochromocytoma: treatment with alpha methyltyrosine for resistant hypertension. J. Pediatr. 91: 143, 1977.PubMedCrossRefGoogle Scholar
  5. 5.
    Scott H.W., Reynolds V., Green N., Page D., Oates J.A., Robertson D., Roberts S. Clinical experience with malignant pheochromocytoma. Surg. Gyneco. I Obstet. 154: 801, 1982.Google Scholar
  6. 6.
    Keiser H.R., Goldstein D.S., Wade J.L., Douglas F.L., Averbuch S.D. Treatment of malignant pheochromocytoma with combination chemotherapy. Hypertension 7(Suppl I): 1–18, 1985.Google Scholar
  7. 7.
    Lewi H.J.E., Reid R., Mucci B., Davidson J.K., Kyle K.F., MacPherson S.G., Semple P., Kaye S. Malignant phaeochromocytoma. Br. J. Urol. 57: 394, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    Averbuch S.D., Steakley C.S., Young R.C., Gelmann E.P., Goldstein D.S., Stull R., Keiser H.R. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann. Intern. Med. 109: 267, 1988.PubMedCrossRefGoogle Scholar
  9. 9.
    Sisson J.C., Frager M.S., Valk T.W., Gross M.D., Swanson D.P., Wieland D.M., Tobes M.C., Beierwaltes W.H., Thompson N.W. Scintigraphic localization of pheochromocytoma. N. Engl.J. Med. 305: 12, 1981.PubMedCrossRefGoogle Scholar
  10. 10.
    Sisson J., Shapiro B., Beierwaltes W.H., Nakajo M., Glowniak J., Mangner T., Carey J.E., Swanson D.P., Copp J., Satterlee W., Wieland D. Treatment of malignant pheochromocytoma with a new radiopharmaceutical. Trans. Assoc. Am. Physicians. 96: 209, 1983.PubMedGoogle Scholar
  11. 11.
    Sisson J.C., Shapiro B., Beierwaltes W.H., Glowniak J.V., Nakajo M., Mangner T.J., Carey J.E., Swanson D.P., Copp J.E., Satterlee W.G., Wieland D.M. Radiopharmaceutical treatment of malignant pheochromocytoma. J. Nucl. Med. 24: 197, 1984.Google Scholar
  12. 12.
    Sisson J.C., Wieland D.M. Radiolabelled meta-iodobenzylguanidine: pharmacology and clinical studies. Am. J. Physiol. Imaging 1: 96, 1986.PubMedGoogle Scholar
  13. 13.
    Thompson N.M., Allo M.D., Shapiro B., Sisson J.C., Beierwaltes W. Extra-adrenal and metastatic pheochromocytoma: the role of 131I meta-iodobenzylguanidine in localization and management. World J.Surg. 8: 605; 1984.PubMedCrossRefGoogle Scholar
  14. 14.
    Shapiro B., Sisson J.C., Eyre P., Copp J.E., Dmuchowski C., Beierwaltes W.H. 131I-MIBG — a new agent in diagnosis and treatment of pheochromocytoma. Cardiology. 72(Suppl I): 137, 1985.PubMedCrossRefGoogle Scholar
  15. 15.
    Khafagi F.A., Shapiro B., Fischer M., Sisson J.C., Hutchinson R., Beierwaltes W.H. Pheochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine. Eur. J. Nuc. Med. 18: 191, 1991.CrossRefGoogle Scholar
  16. 16.
    Krempf M., Lumbroso J., Mornex R., Brendel A.J., Wemeau J.L., Delisle M.J., Aubert B., Carpentier P., Fleury-Goyon M.C., Gibold C., Guyot M., Lahneche B., Marchandise X., Schlumberger M., Charbonnel B., Chatal J.F. Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma. J. Clin. Endocrinol. Metab. 72: 455, 1991.PubMedCrossRefGoogle Scholar
  17. 17.
    Krempf M., Lumbroso J., Mornex R., Brendel A.J., Wemeau J.L., Delisle M.J., Aubert B., Carpentier P., Fleury-Goyon M.C., Gibold C., Guyot M., Lahneche B., Marchandise X., Schlumberger M., Charbonnel B., Chatal J.F. Treatment of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: a French multicenter study. J. Nucl. Biol. Med. 35: 284, 1991.PubMedGoogle Scholar
  18. 18.
    Mornex R., Badet C., Peyrin L. Malignant pheochromocytoma: a series of 14 cases observed between 1966 and 1990. J. Endocrinol. Invest. 15: 643, 1992.PubMedCrossRefGoogle Scholar
  19. 19.
    Brendel A.J., Jeandot R., Guyot M., Lambert B., Drouillard J. Radionuclide therapy of pheochromocytomas and neuroblastomas using iodine-131 metaiodobenzylguanidine (MIBG). Clin. Nucl. Med. 14: 19, 1989.PubMedCrossRefGoogle Scholar
  20. 20.
    Schlumberger M., Gicquel C., Lumbroso J., Tenenbaum F., Comoy E., Bosq J., Fonseca E., Ghillani P.P., Aubert B., Travagli J.P., Gardet P., Parmentier C. Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. J. Endocrinol. Invest. 15: 631, 1992.PubMedCrossRefGoogle Scholar
  21. 21.
    Schvartz C., Gibold C., Vuillemin B., Delisle M.J. Results of [131I]metaiodobenzylguanidine therapy administered to three patients with malignant pheochromocytoma. J. Nucl. Biol. Med. 35: 305, 1991.PubMedGoogle Scholar
  22. 22.
    Pujol P., Bringer J., Faurous P., Jaffiol C. Metastatic pheochromocytoma with a long-term response after iodine-131 metaiodobenzylguanidine therapy. Eur. J. Nucl. Med. 22: 382, 1995.PubMedCrossRefGoogle Scholar
  23. 23.
    Fisher M. Therapy of pheochromocytoma with [131 I]metaiodobenzylguanidine. J. Nucl. Biol. Med. 35: 292, 1991.Google Scholar
  24. 24.
    Vetter H., Fischer M., Muller-Rensing R., Vetter W., Winterberg B. [131I]-meta-iodobenzylguanidine in treatment of malignant pheochromocytomas. Lancet. 2: 107, 1983.PubMedCrossRefGoogle Scholar
  25. 25.
    Lewington V.J., Zivanovic M.A., Tristam M., McEwan A.J.B., Ackery D.M. Radiolabelled metaiodobenzylguanidine targeted radiotherapy for malignant phaeochromocytoma. J. Nucl. Biol. Med. 35: 280, 1991.PubMedGoogle Scholar
  26. 26.
    Bomanji J., Britton K.E., Ur E., Hawkins L., Grossman A.B., Besser G.M. Treatment of malignant phaeochromocytoma, paraganglioma and carcinoid tumours with 131I-metaiodobenzylguanidine. Nucl. Med. Commun. 14: 856, 1993.PubMedCrossRefGoogle Scholar
  27. 27.
    Bestagno M., Pizzocaro C., Maira G., Terzi A., Panarotto M.B., Guerra P. Results of [131I]metaiodobenzylguanidine treatment in metastatic malignant phaeochromocytoma. J. Nucl. Biol. Med. 35: 277, 1991.PubMedGoogle Scholar
  28. 28.
    Trocone L., Rufini V., Montemaggi P., Danza F.M., Lasorella A., Mastrangelo R. The diagnostic and therapeutic utility of radioiodinated metaiodobenzylguanidine. Eur. J. Nucl. Med. 16: 325, 1990.CrossRefGoogle Scholar
  29. 29.
    Trocone L., Rufini V., Daidone M.S., De Santis M., Luzi S. [131I]metaiodobenzylguanidine treatment of malignant pheochromocytoma: experience of the Rome group. J. Nucl. Biol. Med. 35: 295, 1991.Google Scholar
  30. 30.
    Colombo L., Lomuscio G., Vignati A., Dottorini M.E. Preliminary results of [131I]metaiodobenzylguanidine treatment in metastatic malignant pheochromocytoma. J. Nucl. Biol. Med. 35: 300, 1991.PubMedGoogle Scholar
  31. 31.
    Limone P., Pogliano G., Castellano G., Argiro G., Isaia G.C., Favero A., Cottino F., Rizzi G., Molinatti G.M. 131-I-meta-iodobenzylguanidine for the diagnosis and treatment of pheochromocytoma. Panminerva Med. 30: 169, 1988.PubMedGoogle Scholar
  32. 32.
    Hoefnagel C.A., Voute P.A., de Kraker J., Marcuse H.R. Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine. J.Nucl. Med. 28: 308, 1987.PubMedGoogle Scholar
  33. 33.
    Voute P.A., Hoefnagel C.A., de Kraker J., Evans A.E., Hayes A., Green A. Radionuclide therapy of neural crest tumors. Med. Pediatr. Oncol. 15: 192, 1987.PubMedCrossRefGoogle Scholar
  34. 34.
    Konings J.E., Bruning P.F., Abeling N.G.G.M., van Gennip A.H., Hoefnagel C.A. Diagnosis and treatment of malignant pheochromocytoma with 1311-meta-iodobenzylguanidine: a case report. Radiother. Oncol. 17: 103, 1990.PubMedCrossRefGoogle Scholar
  35. 35.
    Hoefnagel C.A., Schornagel J., Valdes Olmos R.A. [131I]metaiodobenzylguanidine therapy of malignant pheochromocytoma: interference of medication. J. Nucl. Biol. Med. 35: 308, 1991.PubMedGoogle Scholar
  36. 36.
    Goncalves E., Ninane J., Wese F.X., Leonet J., Piret L., Cornu G., De Meyer R. Familial phaeochromocytoma: successful treatment with 131I-MIBG. Med. Pediatr. Oncol. 18: 126, 1990.PubMedCrossRefGoogle Scholar
  37. 37.
    Theilade K., Bak M., Olsen K., Nielsen S.L., Christensen N.J. A case of malignant pheochromocytoma treated by 131 I-metaiodobenzylguanidine. Acta Oncol. 27: 296, 1988.PubMedCrossRefGoogle Scholar
  38. 38.
    Sakahara H., Endo K., Saga T., Hosono M., Kobayashi H., Konishi J. 131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma. Ann. Nucl. Med. 8: 133, 1994.PubMedCrossRefGoogle Scholar
  39. 39.
    Nakagami Y., Nomura K., Kusakabe K., Miko N., Tsushima T., Demura H. A case of malignant pheochromocytoma treated with 131I-metaiodobenzylguanidine and alpha-methyl-p-tyrosine. Jpn. J. Med. 29: 329, 1990.PubMedCrossRefGoogle Scholar
  40. 40.
    Sasaki M., Iwaoka T., Yamauchi J., Tokunaga H., Naomi S., Inoue J., Oishi S., Umeda T., Sato T. A case of Sipple’s syndrome with malignant pheochromocytoma treated with 131I-metaiodobenzyl guanidine and a combined chemotherapy with cyclophosphamide, incristine and dacarbazine. Endocr. J. 41: 155, 1994.PubMedCrossRefGoogle Scholar
  41. 41.
    Guo J.Z., Gong L.S., Chen S.X., Luo B.Y., Xu M.Y. Malignant pheochromocytoma: diagnosis and treatment in fifteen cases. J. Hypertens. 7: 261, 1989.PubMedCrossRefGoogle Scholar
  42. 42.
    Hoefnagel C.A., Voute P.A., de Kraker J., Marcuse H.R. Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine. J.Nucl. Med. 28: 308, 1987.PubMedGoogle Scholar
  43. 43.
    Beierwaltes W.H. Update on basic research and clinical experience with metaiodobenzylguanidine. Med. Pediatr. Oncol. 15: 163, 1987.PubMedCrossRefGoogle Scholar
  44. 44.
    Mastrangelo R., Lasorella A., Iavarone A., Rufini V., Troncone L., Danza F., Riccardi R. Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis. Med. Pediatr. Oncol, 21: 411, 1993.PubMedCrossRefGoogle Scholar
  45. 45.
    Miller A.B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 47: 207, 1981.PubMedCrossRefGoogle Scholar
  46. 46.
    Hoefnagel C.A. Radionuclide therapy revisited. Eur. J. Nucl. Med. 18: 408, 1991.PubMedCrossRefGoogle Scholar
  47. 47.
    Koral K.F., Wang X.H., Sisson J.C., Botti J., Meyer L., Mallette S., Glazer G.M., Adler R.S. Calculating radiation absorbed dose for pheochromocytoma tumors in 131ImIBG therapy. J. Rad. Oncol. Biol. 17: 211, 1989.CrossRefGoogle Scholar
  48. 48.
    Vaidyanathan G., Zalutsky M.R. No-carrier-added synthesis of meta-[131I]iodobenzylguanidine. Appl Radiat Isot (Int. J. Rad. Appl Instrum. [A]. 44: 621, 1993.Google Scholar
  49. 49.
    Mangner J.T., Wu J.-L., Wieland D.M. Solid-phase exchange radioiodination of aryl iodides: facilitation by ammonium sulfate. J.Org.Chem. 47: 1484, 1982.CrossRefGoogle Scholar
  50. 50.
    Mairs R.J., Cunningham S.H., Russell J., Armour A., Owens J., McKellar K., Gaze M.N. No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation. J. Nucl. Med. 36: 1088, 1995.PubMedGoogle Scholar
  51. 51.
    Mairs R.J., Russell J., Cunningham S., O’Donoghue J.A., Gaze M.N., Owens J., Vaidyanathan G., Zalutsky, M.R. Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I] meta-iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma. Eur. J. Cancer. 31A: 576, 1995.PubMedCrossRefGoogle Scholar
  52. 52.
    Sisson J.C., Hutchinson R.J., Carey J.E., Shapiro B., Johnson J.W., Mallette SA, Wieland DM. Toxicity from treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Eur. J. Nucl. Med. 14: 337, 1988.PubMedGoogle Scholar
  53. 53.
    Blake G.M., Lewington V.J., Fleming J.S., Zivanovic M.A., Ackery D.M. Modification by nifedipine of 131I-meta-iodobenzylguanidine kinetics in malignant pheochromocytoma. Eur. J. Nucl. Med. 14: 345, 1988.PubMedGoogle Scholar
  54. 54.
    Khafagi F.A., Shapiro B., Fig L.M., Mallette S., Sisson J.C. Labetalol reduces iodine-131-MIBG uptake by pheochromocytoma and normal tissues. J.Nucl. Med. 30: 481, 1989.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1997

Authors and Affiliations

  • Keh-Chuan Loh
    • 1
    • 4
  • P. A. Fitzgerald
    • 1
  • K. K. Matthay
    • 2
  • P. P. B. Yeo
    • 1
  • D. C. Price
    • 3
  1. 1.Division of Endocrinology & Metabolism, Department of Medicine & Metabolic Research UnitUniversity of California at San FranciscoSan FranciscoUSA
  2. 2.Division of Hematology-Oncology, Department of PediatricsUniversity of California at San FranciscoSan FranciscoUSA
  3. 3.Nuclear Medicine Program, Department of RadiologyUniversity of California at San FranciscoSan FranciscoUSA
  4. 4.Department of MedicineTan Tock Seng HospitalSingaporeRepublic of Singapore

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