Utility of 123I-MIBG Standardized Uptake Value in Patients with Refractory Pheochromocytoma and Paraganglioma

Document Type : Original Article

Authors

1 Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa, Japan

2 Department of Radiological Technology, Kanazawa University Hospital, Kanazawa, Japan

Abstract

Objective(s): Single-photon emission computed tomography (SPECT) using metaiodobenzylguanidine (MIBG) is an important diagnostic tool for the treatment of refractory pheochromocytoma and paraganglioma (PPGL). Owing to the difficulty of SPECT quantification, the tumour-to-background ratio (TBR) is used to assess disease activity. However, the utility of TBR is limited owing to the background setting. A quantification technique of SPECT/computed tomography (CT) would facilitate image interpretation. This study aimed to assess the relationship between 123I-MIBG maximum standardized uptake value (SUVmax) and TBR and levels of urinary catecholamines and metabolites in patients with refractory PPGL.
Methods: This study included 15 patients with refractory PPGL who underwent 131I-MIBG therapy. Overall, 27 123I-MIBG SPECT/CT images were acquired before and after the therapy. Lesions observed on whole-body images were analysed; the maximum number of lesions per scan was 10. 123I-MIBG SUVmax was semi-automatically calculated using Q. Metrix package (GE Healthcare). TBR was manually calculated according to the following formula: (max count in lesion − max count in background)/max count in background. Background was set in the contralateral area. When a background region of interest could not be set in the area, it was set in the thigh area. Urine was sampled for 24 h to measure catecholamine and metabolite levels. Increases of ≥3-fold were considered abnormal. TBR, 123I-MIBG SUVmax and urinary catecholamine and metabolite levels were compared using linear regression analysis.
Results: All patients had MIBG-avid lesions, as seen on 123I-MIBG SPECT/CT. A significant relationship between 123I-MIBG SUVmax and TBR was observed (correlation coefficient [r] =0.84, P < 0.0001). In 27 SPECT/CT examinations, normetanephrine (NMN) level was abnormally increased in 51% (14/27), but other catecholamine and other metabolites were abnormally increased in < 26% (7/27). 123I-MIBG SUVmax strongly correlated with NMN (r=0.76, P < 0.01) and log NMN (r=0.74, P < 0.01).
Conclusion: 123I-MIBG SUVmax demonstrated similar trends as TBR and reflected urinary NMN in patients with refractory PPGL. Semi-automatic quantification of SPECT/CT could be a useful tool for the evaluation of disease activity

Keywords

Main Subjects


  1. Taieb D, Timmers HJ, Hindie E, Guillet BA, Neumann HP, Walz MK, et al. EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2012;39(12):1977-95.
  2. Rufini V, Treglia G, Perotti G, Giordano A. The evolution in the use of MIBG scintigraphy in pheochromocytomas and paragangliomas. Hormones. 2013;12(1):58-68.
  3. Bomanji J, Levison DA, Flatman WD, Horne T, Bouloux PM, Ross G, et al. Uptake of iodine-123 MIBG by pheochromocytomas, paragangliomas, and neuroblastomas: a histopathological comparison. J Nucl Med. 1987;28(6):973-8.
  4. Vaidyanathan G. Meta-iodobenzylguanidine and analogues: chemistry and biology. Q J Nucl Med Mol Imaging. 2008;52(4):351-68.
  5. Willowson K, Bailey D, Schembri G, Baldock C. CT-based quantitative SPECT for the radionuclide 201Tl: experimental validation and a standardized uptake value for brain tumour patients. Cancer Imaging. 2012;12(1):31-40.
  6. Collarino A, Pereira Arias-Bouda LM, Valdes Olmos RA, van der Tol P, Dibbets-Schneider P, de Geus-Oei LF, et al. Experimental validation of absolute SPECT/ CT quantification for response monitoring in breast cancer. Med Phys. 2018;45(5):2143-53.
  7. Yamane T, Kuji I, Seto A, Matsunari I. Quantification of osteoblastic activity in epiphyseal growth plates by quantitative bone SPECT/CT. Skeletal Radiol. 2018;47(6):805-10.
  8. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-42.
  9. van Berkel A, Rao JU, Lenders JW, Pellegata NS, Kusters B, Piscaer I, et al. Semiquantitative 123I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiologic adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters. J Nucl Med. 2015;56(6):839-46.
  10. Mozley PD, Kim CK, Mohsin J, Jatlow A, Gosfield E, Alavi A. The efficacy of iodine-123-MIBG as a screening-test for pheochromocytoma. J Nucl Med. 1994;35(7):1138-44.
  11. Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR, et al. Malignant pheochromocytoma: current status and initiatives for future progress. Endocr Relat Cancer. 2004;11(3):423-36.
  12. Fiebrich HB, Brouwers AH, 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-metaiodobenzylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess. J Clin Endocrinol Metab. 2009;94(10):3922-30.
  13. Eisenhofer G, Goldstein DS, Kopin IJ, Crout JR. Pheochromocytoma: rediscovery as a catecholamine-metabolizing tumor. Endocr Pathol. 2003;14(3):193-212.
  14. Moog S, Houy S, Chevalier E, Ory S, Weryha G, Rame M, et al. 18F-FDOPA PET/CT uptake parameters correlate with catecholamines secretion in human pheochromocytomas. Neuroendocrinology. 2018; 107(3):228-36.
  15. Steyn R, Prasad V. Does Somatostatin Receptor (SSR) positive tumor volume determined on Ga68 DOTANOC PET/CT in patients with paraganglioma (PGL)/pheochromocytoma (PCC) correlate with biomarkers? An explorative study. Neuroendocrinology. 2018;106:259.
  16. Tan TH, Hussein Z, Saad FF, Shuaib IL. Diagnostic performance of (68)Ga-DOTATATE PET/CT, (18) F-FDG PET/CT and (131)I-MIBG scintigraphy in mapping metastatic pheochromocytoma and paraganglioma. Nucl Med Mol Imaging. 2015;49(2):143-51.
  17. Fonte JS, Robles JF, Chen CC, Reynolds J, Whatley M, Ling A, et al. False-negative 123I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease. Endocr Relat Cancer. 2012;19(1):83-93.
  18. Bailey DL, Willowson KP. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med. 2013;54(1):83-9.