Der Nuklearmediziner 2019; 42(01): 27-35
DOI: 10.1055/a-0807-3574
Theranostik
© Georg Thieme Verlag KG Stuttgart · New York

Nuklearmedizinische Therapie von Nebennierentumoren

Radionuclide Therapy of Adrenal Tumors
Michael C. Kreißl
Bereich Nuklearmedizin, Universitätsklinik für Radiologie und Nuklearmedizin, Universität Magdeburg, Magdeburg
,
Philipp Genseke
Bereich Nuklearmedizin, Universitätsklinik für Radiologie und Nuklearmedizin, Universität Magdeburg, Magdeburg
› Author Affiliations
Further Information

Publication History

Publication Date:
25 April 2019 (online)

Zusammenfassung

In der Nebenniere liegen 2 distinkt unterschiedliche Gewebe, das Nebennierenmark und die Nebennierenrinde vor. Beide Gewebearten sezernieren unterschiedliche Hormone und besitzen eigene molekulare Charakteristika, die für eine spezifische Bildgebung mit Radiotracern genutzt werden können. Für das Nebennierenmark sind dies der Noradrenalin-Re-Uptake-Transporter und, beschränkt, auch der Somatostatinrezeptor. Für die Nebennierenrinde ist eine spezifische Darstellung von Enzymen der Cortisol- und Aldosteronbiosynthese möglich. In theranostischen Ansätzen wurden alle Zielstrukturen bisher bereits für gezielte Radionuklidtherapien genutzt, jedoch ist bisher lediglich die Noradrenalin-Re-Uptake-Transporter-gezielte 131I-metaIodBenzylGuanidin (mIBG)-Behandlung klinisch etabliert.

Abstract

In the adrenal glands, 2 distinctly different types of tissue may be found, adrenal medulla and the cortex. Both tissues produce different hormones and have their own molecular characteristics, which may be targeted for a specific imaging using radiotracers. For the adrenal medulla, these are the norepinephrine reuptake transporter and, with limitations, also the somatostatin receptor. For the adrenal cortex, a specific visualisation may be achieved by imaging enzymes involved in the cortisol and aldosterone biosynthesis. In a theranostic setting, all target structures have so far been addressed in the context of radionuclide therapies, but only the treatment with 131I-metaIodBenzylGuanidin (mIBG) targeting the noradrenalin reuptake transporter has found its way into clinical routine.

 
  • Literatur

  • 1 Gaujoux S, Mihai R. et al. Joint working group of ESES and ENSAT. European Society of Endocrine Surgeons (ESES) and European Network for the Study of Adrenal Tumours (ENSAT) recommendations for the surgical management of adrenocortical carcinoma. Br J Surg 2017; 104: 358-376
  • 2 Fassnacht M, Dekkers OM, Else T. et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. European journal of endocrinology 2018; 179: G1-G46
  • 3 Kroiss AS. Current status of functional imaging in neuroblastoma, pheochromocytoma, and paraganglioma disease. Wien Med Wochenschr 2019; 169: 25-32
  • 4 Wieland DM, Swanson DP, Brown LE. et al. Imaging the adrenal medulla with an I-131-labeled antiadrenergic agent. J Nucl Med 1979; 20: 155-158
  • 5 Lashford LS, Hancock JP, Kemshead JT. Meta-iodobenzylguanidine (mIBG) uptake and storage in the human neuroblastoma cell line SK-N-BE(2C). Int J Cancer 1991; 47: 105-109
  • 6 Kolby L, Bernhardt P, Levin-Jakobsen AM. et al. Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters. Br J Cancer 2003; 89: 1383-1388
  • 7 Bomanji J, Levison DA, Flatman WD. et al. Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison. J Nucl Med 1987; 28: 973-978
  • 8 Quint LE, Glazer GM, Francis IR. et al. Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and I-131 MIBG scintigraphy. Radiology 1987; 165: 89-93
  • 9 Wiseman GA, Pacak K, O'Dorisio MS. et al. Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial. J Nucl Med 2009; 50: 1448-1454
  • 10 Watanabe S, Hanaoka H, Liang JX. et al. PET imaging of norepinephrine transporter-expressing tumors using 76Br-meta-bromobenzylguanidine. J Nucl Med 2010; 51: 1472-1479
  • 11 Cistaro A, Quartuccio N, Caobelli F. et al. 124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma. Nucl Med Rev Cent East Eur 2015; 18: 102-106
  • 12 Hartung-Knemeyer V, Rosenbaum-Krumme S, Buchbender C. et al. Malignant pheochromocytoma imaging with [124I]mIBG PET/MR. The Journal of clinical endocrinology and metabolism 2012; 97: 3833-3834
  • 13 Vaidyanathan G, Affleck DJ, Zalutsky MR. (4-[18F]fluoro-3-iodobenzyl)guanidine, a potential MIBG analogue for positron emission tomography. J Med Chem 1994; 37: 3655-3662
  • 14 Pandit-Taskar N, Zanzonico P, Staton KD. et al. Biodistribution and Dosimetry of (18)F-Meta-Fluorobenzylguanidine: A First-in-Human PET/CT Imaging Study of Patients with Neuroendocrine Malignancies. J Nucl Med 2018; 59: 147-153
  • 15 Kushner BH, Cheung NK. Exploiting the MIBG-avidity of neuroblastoma for staging and treatment. Pediatr Blood Cancer 2006; 47: 863-864
  • 16 Brisse HJ, McCarville MB, Granata C. et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology 2011; 261: 243-257
  • 17 AWMF. Langfassung der Leitlinie "Tumor-Szintigraphie mit 123-Iod-(131-I)-meta-Iodbenzylguanidin (mBIG)". 2015
  • 18 Labreveux de Cervens C, Hartmann O, Bonnin F. et al. What is the prognostic value of osteomedullary uptake on MIBG scan in neuroblastoma patients under one year of age?. Med Pediatr Oncol 1994; 22: 107-114
  • 19 Schmidt M, Simon T, Hero B. et al. The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma > 1 year of age on a high-risk treatment protocol: results of the German Neuroblastoma Trial NB97. Eur J Cancer 2008; 44: 1552-1558
  • 20 Katzenstein HM, Cohn SL, Shore RM. et al. Scintigraphic response by 123I-metaiodobenzylguanidine scan correlates with event-free survival in high-risk neuroblastoma. J Clin Oncol 2004; 22: 3909-3915
  • 21 Papathanasiou ND, Gaze MN, Sullivan K. et al. 18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis. J Nucl Med 2011; 52: 519-525
  • 22 Troncone L, Rufini V, Danza FM. et al. Radioiodinated metaiodobenzylguanidine (*I-MIBG) scintigraphy in neuroblastoma: a review of 160 studies. J Nucl Med Allied Sci 1990; 34: 279-288
  • 23 Feine U, Muller-Schauenburg W, Treuner J. et al. Metaiodobenzylguanidine (MIBG) labeled with 123I/131I in neuroblastoma diagnosis and follow-up treatment with a review of the diagnostic results of the International Workshop of Pediatric Oncology held in Rome, September 1986. Med Pediatr Oncol 1987; 15: 181-187
  • 24 Kushner BH, Yeh SD, Kramer K. et al. Impact of metaiodobenzylguanidine scintigraphy on assessing response of high-risk neuroblastoma to dose-intensive induction chemotherapy. J Clin Oncol 2003; 21: 1082-1086
  • 25 Matthay KK, Shulkin B, Ladenstein R. et al. Criteria for evaluation of disease extent by (123)I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 2010; 102: 1319-1326
  • 26 Ady N, Zucker JM, Asselain B. et al. A new 123I-MIBG whole body scan scoring method--application to the prediction of the response of metastases to induction chemotherapy in stage IV neuroblastoma. Eur J Cancer 1995; 31A: 256-261
  • 27 Messina JA, Cheng SC, Franc BL. et al. Evaluation of semi-quantitative scoring system for metaiodobenzylguanidine (mIBG) scans in patients with relapsed neuroblastoma. Pediatr Blood Cancer 2006; 47: 865-874
  • 28 Radovic B, Artiko V, Sobic-Saranovic D. et al. Evaluation of the SIOPEN semi-quantitative scoring system in planar simpatico-adrenal MIBG scintigraphy in children with neuroblastoma. Neoplasma 2015; 62: 449-455
  • 29 Pandit-Taskar N, Modak S. Norepinephrine Transporter as a Target for Imaging and Therapy. J Nucl Med 2017; 58: 39S-53S
  • 30 Safford SD, Coleman RE, Gockerman JP. et al. Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma. Surgery 2003; 134: 956-962 ; discussion 962-953
  • 31 Castellani MR, Seghezzi S, Chiesa C. et al. (131)I-MIBG treatment of pheochromocytoma: low versus intermediate activity regimens of therapy. The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine 2010; 54: 100-113
  • 32 Yoshinaga K, Oriuchi N, Wakabayashi H. et al. Effects and safety of 131I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry. Endocr J 2014; 61: 1171-1180
  • 33 Gonias S, Goldsby R, Matthay KK. et al. Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol 2009; 27: 4162-4168
  • 34 Loh KC, Fitzgerald PA, Matthay KK. et al. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients. J Endocrinol Invest 1997; 20: 648-658
  • 35 Carrasquillo JA, Pandit-Taskar N, Chen CC. I-131 Metaiodobenzylguanidine Therapy of Pheochromocytoma and Paraganglioma. Semin Nucl Med 2016; 46: 203-214
  • 36 Matthay KK, Quach A, Huberty J. et al. Iodine-131-metaiodobenzylguanidine double infusion with autologous stem-cell rescue for neuroblastoma: a new approaches to neuroblastoma therapy phase I study. J Clin Oncol 2009; 27: 1020-1025
  • 37 Modak S, Zanzonico P, Carrasquillo JA. et al. Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study. J Nucl Med 2016; 57: 231-237
  • 38 French S, DuBois SG, Horn B. et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer 2013; 60: 879-884
  • 39 DuBois SG, Allen S, Bent M. et al. Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma. Br J Cancer 2015; 112: 644-649
  • 40 DuBois SG, Groshen S, Park JR. et al. Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res 2015; 21: 2715-2721
  • 41 Mastrangelo S, Tornesello A, Diociaiuti L. et al. Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy. Br J Cancer 2001; 84: 460-464
  • 42 Matthay KK, Tan JC, Villablanca JG. et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol 2006; 24: 500-506
  • 43 Matthay KK, Yanik G, Messina J. et al. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. J Clin Oncol 2007; 25: 1054-1060
  • 44 Matthay KK, Weiss B, Villablanca JG. et al. Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. J Nucl Med 2012; 53: 1155-1163
  • 45 Treuner J, Klingebiel T, Feine U. et al. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Pediatr Hematol Oncol 1986; 3: 205-216
  • 46 Chin BB, Kronauge JF, Femia FJ. et al. Phase-1 clinical trial results of high-specific-activity carrier-free 123I-iobenguane. J Nucl Med 2014; 55: 765-771
  • 47 Noto RB, Pryma DA, Jensen J. et al. Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma. The Journal of clinical endocrinology and metabolism 2018; 103: 213-220
  • 48 Vaidyanathan G, Strickland DK, Zalutsky MR. Meta-[211At]astatobenzylguanidine: further evaluation of a potential therapeutic agent. Int J Cancer 1994; 57: 908-913
  • 49 Vaidyanathan G, Friedman HS, Keir ST. et al. Evaluation of meta-[211At]astatobenzylguanidine in an athymic mouse human neuroblastoma xenograft model. Nucl Med Biol 1996; 23: 851-856
  • 50 Gaze MN, Chang YC, Flux GD. et al. Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma. Cancer Biother Radiopharm 2005; 20: 195-199
  • 51 More SS, Itsara M, Yang X. et al. Vorinostat increases expression of functional norepinephrine transporter in neuroblastoma in vitro and in vivo model systems. Clin Cancer Res 2011; 17: 2339-2349
  • 52 McCluskey AG, Boyd M, Pimlott SL. et al. Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination. Br J Radiol 2008; 81 Spec No 1 S28-35
  • 53 Raggi CC, Maggi M, Renzi D. et al. Quantitative determination of sst2 gene expression in neuroblastoma tumor predicts patient outcome. The Journal of clinical endocrinology and metabolism 2000; 85: 3866-3873
  • 54 Maggi M, Baldi E, Finetti G. et al. Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines. Cancer Res 1994; 54: 124-133
  • 55 Moertel CL, Reubi JC, Scheithauer BS. et al. Expression of somatostatin receptors in childhood neuroblastoma. Am J Clin Pathol 1994; 102: 752-756
  • 56 Orlando C, Raggi CC, Bagnoni L. et al. Somatostatin receptor type 2 gene expression in neuroblastoma, measured by competitive RT-PCR, is related to patient survival and to somatostatin receptor imaging by indium -111-pentetreotide. Med Pediatr Oncol 2001; 36: 224-226
  • 57 Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003; 24: 389-427
  • 58 Reubi JC, Waser B, Schaer JC. et al. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med 2001; 28: 836-846
  • 59 Mundschenk J, Unger N, Schulz S. et al. Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy. The Journal of clinical endocrinology and metabolism 2003; 88: 5150-5157
  • 60 Han S, Suh CH, Woo S. et al. Performance of (68)Ga-DOTA-Conjugated Somatostatin Receptor Targeting Peptide PET in Detection of Pheochromocytoma and Paraganglioma: A Systematic Review and Meta-Analysis. J Nucl Med 2018; DOI: 10.2967/jnumed.118.211706.
  • 61 Kong G, Hofman MS, Murray WK. et al. Initial Experience With Gallium-68 DOTA-Octreotate PET/CT and Peptide Receptor Radionuclide Therapy for Pediatric Patients With Refractory Metastatic Neuroblastoma. J Pediatr Hematol Oncol 2016; 38: 87-96
  • 62 Gains JE, Bomanji JB, Fersht NL. et al. 177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma. J Nucl Med 2011; 52: 1041-1047
  • 63 Forrer F, Riedweg I, Maecke HR. et al. Radiolabeled DOTATOC in patients with advanced paraganglioma and pheochromocytoma. The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine 2008; 52: 334-340
  • 64 Kong G, Grozinsky-Glasberg S, Hofman MS. et al. Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma. The Journal of clinical endocrinology and metabolism 2017; 102: 3278-3287
  • 65 Nakajo M, Nakabeppu Y, Yonekura R. et al. The role of adrenocortical scintigraphy in the evaluation of unilateral incidentally discovered adrenal and juxtaadrenal masses. Ann Nucl Med 1993; 7: 157-166
  • 66 Hwang I, Balingit AG, Georgitis WJ. et al. Adrenocortical SPECT using iodine-131 NP-59. J Nucl Med 1998; 39: 1460-1463
  • 67 Hahner S, Stuermer A, Kreissl M. et al. [123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. The Journal of clinical endocrinology and metabolism 2008; 93: 2358-2365
  • 68 Hennings J, Lindhe O, Bergstrom M. et al. [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings. The Journal of clinical endocrinology and metabolism 2006; 91: 1410-1414
  • 69 Erlandsson M, Karimi F, Lindhe O. et al. (18)F-labelled metomidate analogues as adrenocortical imaging agents. Nucl Med Biol 2009; 36: 435-445
  • 70 Hahner S, Kreissl MC, Fassnacht M. et al. Functional characterization of adrenal lesions using [123I]IMTO-SPECT/CT. The Journal of clinical endocrinology and metabolism 2013; 98: 1508-1518
  • 71 Kreissl MC, Schirbel A, Fassnacht M. et al. [(1)(2)(3)I]Iodometomidate imaging in adrenocortical carcinoma. The Journal of clinical endocrinology and metabolism 2013; 98: 2755-2764
  • 72 Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab 2009; 23: 273-289
  • 73 Assie G, Antoni G, Tissier F. et al. Prognostic parameters of metastatic adrenocortical carcinoma. The Journal of clinical endocrinology and metabolism 2007; 92: 148-154
  • 74 Hahner S, Fassnacht M. Mitotane for adrenocortical carcinoma treatment. Curr Opin Investig Drugs 2005; 6: 386-394
  • 75 Fassnacht M, Terzolo M, Allolio B. et al. Combination chemotherapy in advanced adrenocortical carcinoma. The New England journal of medicine 2012; 366: 2189-2197
  • 76 Hahner S, Kreissl MC, Fassnacht M. et al. [131I]iodometomidate for targeted radionuclide therapy of advanced adrenocortical carcinoma. The Journal of clinical endocrinology and metabolism 2012; 97: 914-922
  • 77 Heinze B, Schirbel A, Herrmann K. et al. [123/131I](R)-1-[1-(4-iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide (IMAZA) – A novel radiotracer for diagnosis and treatment of adrenocortical tumours – From bench to bedside. Exp Clin Endocrinol Diabetes 2015; DOI: 10.1055/s-0035-1547710.
  • 78 Michelmann D. In vitro und in vivo Evaluation von Iodmetomidat-Carbonsäureamid-Derivaten für die Diagnostik und Therapie von Nebennierenkarzinomen. Würzburg: Julius-Maximilians-Universität Würzburg; 2017: 85