Incremental value of ^99mTc-HYNICTOC SPECT/CT over whole-body planar scintigraphy and SPECT in patients with neuroendocrine tumours

Summary

Aim: The aim of this study was to evaluate the additional value of ^99mTc-HYNIC-TOC SPECT/CT over planar whole-body (WB) scintigraphy and SPECT alone in the detection and accurate localisation of neuroendocrine tumour (NET) lesions. Methods: This study included 65 patients with a definitive histological diagnosis of NET prior to scintigraphy. Planar WB scintigraphy, SPECT, and SPECT/CT images were acquired at 4 h postadministration of 670 MBq ^99mTc-HYNIC- TOC. Additional SPECT images at 10 min after tracer administration were also acquired. Clinical and imaging follow-up findings were considered as the reference standards (minimum follow-up period, 15 months). Patient and lesion-based analyses of the efficacies of the imaging modalities were performed. Results: While 38 patients exhibited metastasis of NETs, 27 presented no evidence of metastasis. Upon patient- based analysis, the sensitivity and specificity of SPECT/CT were found to be 88.9 and 79.3 %, respectively. The diagnostic accuracies of WB scintigraphy, 4h-SPECT, and SPECT/CT were 72.3, 73.8, and 84.6 %o, respectively. The area under curve (AUC) value for SPECT/CT (0.84) was the highest, followed by those for 4h-SPECT (0.75) and WB scintigraphy (0.74). The accuracy and AUC values of SPECT/CT were significantly better compared to those of WB scintigraphy (p < 0.001), 10 min-SPECT (p < 0.001), and 4 h-SPECT (p = 0.001). The findings of SPECT/CT led to the change in treatment plan of 11 patients (16.9 %o). Conclusion: The sensitivity and diagnostic accuracy of SPECT/CT in the evaluation of NET lesions outperforms planar WB imaging or SPECT alone.

Zusammenfassung

Ziel: Das Ziel dieser Studie war den Mehrwert von ^99mTc-HYNIC-TOC SPECT/CT gegenüber planarer Ganzkörper-Szintigraphie (GK) und SPECT alleine zur Erkennung und genauen Lokalisation von Läsionen bei neuroendokri- nen Tumoren (NET) zu untersuchen. Methoden: Diese Studie umfasste 65 Patienten mit einer vor der Szintigraphie histologisch gesicherten Diagnose von NET. Planare-GK-Szin- tigraphie, SPECT und SPECT/CT wurden 4 Stunden nach der Verabreichung von 670 MBq ^99mTc-HYNIC-TOC durchgeführt. Zusätzliche SPECT-Bilder 10 min nach der Radiopharmakon-Applikation wurden ebenfalls aufgenommen. Als Referenzstandards dienten die klinischen und Imaging-Follow-up-Er- gebnisse (Mindest-Follow-up-Zeitraum: 15 Monate). Patienten- und Läsions-basierte Analysen des diagnostischen Wertes der Bild- gebungsmodalitäten wurden durchgeführt. Ergebnisse: 38 Patienten hatten Metastasen. 27 zeigten kein Hinweis auf eine Metastasierung. Die Patienten-basierte Analyse bei SPECT/CT ergab eine Sensitivität von 88,9 °% und Spezifität von 79,3 °%. Die diagnostische Genauigkeit der GK-Szintigraphie, SPECT-4h bzw. SPECT/CT war 72,3, 73,8 bzw. 84,6 %. Der AUC-Wert (Area under the curve) war für SPECT/CT am höchsten. Die Genauigkeit und AUC-Werte der SPECT/CT waren signifikant höher als die Werte von GK-Szintigraphie (p < 0,001), 10 min-SPECT (p < 0,001) und 4 h-SPECT (p = 0,001). Die Ergebnisse der SPECT/CT führten zu Änderungen im Behandlungsplan bei 11 Patienten (16,9 °%). Schlussfolgerung: Die SPECT/CT zeigte bei der Beurteilung von NET-Läsionen eine höhere Sensi- tivität und diagnostische Genauigkeit als GK- Szintigraphie und SPECT alleine.

Keywords

neuroendocrine tumours - receptors somatostatin - technetium 99m EDDA-HYNIC-Tyr(3)-octreotide

Schlüsselwörter

neuroendokrine Tumoren - Somatostatin-Rezeptor-Szintigraphie - Technetium 99m EDDAHYNIC-Tyr (3)-Octreotid

• References

• 1 Albanus DR, Apitzsch J, Erdern Z. et al. Clinical value of (68)Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). Eur J Radiol 2015; 84: 1866-1872.
• 2 Balon HR, Goldsmith SJ, Siegel BA. et al. Procedure guideline for somatostatin receptor scintigraphy with (111)In-pentetreotide. J Nucl Med 2001; 42: 1134-1138.
• 3 Bangard M, Béhé M, Guhlke S. et al. Detection of somatostatin receptor-positive tumours using the new ^99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide. Eur J Nucl Med 2000; 27: 628-637.
• 4 Breeman WA, de Blois E, Sze Chan H. et al. (68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives. Semin Nucl Med 2011; 41: 314-321.
• 5 Decristoforo C, Mather SJ, Cholewinski W. et al. ^99mTc-EDDA/HYNIC-TOC: a new ^99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with ¹¹¹In-labelled octreotide derivatives. Eur J Nucl Med 2000; 27: 1318-1325.
• 6 Decristoforo C, Melendez-Alafort L, Sosabowski JK. et al. ^99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with ¹¹¹In-octreotide. J Nucl Med 2000; 41: 1114-1119.
• 7 Etchebehere EC, de Oliveira Santos A, Gumz B. et al. ⁶⁸Ga-DOTATATE PET/CT, ^99mTc-HYNIC-octreotide SPECT/CT, and whole-body MR imaging in detection of neuroendocrine tumors: a prospective trial. J Nucl Med 2014; 55: 1598-1604.
• 8 Gabriel M, Muehllechner P, Decristoforo C. et al. ^99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors. Q J Nucl Med Mol Imaging 2005; 49: 237-244.
• 9 Gabriel M, Decristoforo C, Donnemiller E. et al. An intrapatient comparison of ^99mTc-EDDA/ HYNIC-TOC with ¹¹¹In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. J Nucl Med 2003; 44: 708-716.
• 10 Gabriel M, Decristoforo C, Kendler D. et al. ⁶⁸Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48: 508-518.
• 11 Gabriel M, Hausler F, Bale R. et al. Image fusion analysis of 99mTc-HYNIC-Tyr3-octreotide SPECT and diagnostic CT using an immobilisation device with external markers in patients with endocrine tumours. Eur J Nucl Med Mol Imaging 2005; 32: 1440-1451.
• 12 Garai I, Barna S, Nagy G. et al. Limitations and pitfalls of Tc-99m-EDDA//HYNIC-TOC (Tektrotyd) scintigraphy. Nucl Med Rev 2016; 19: 93-98.
• 13 Gonzalez-Vazquez A, Ferro-Flores G, Arteaga de Murphy C. et al. Biokinetics and dosimetry in patients of ^99mTc-EDDA/HYNIC-Tyr3-octreotide prepared from lyophilized kits. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 2006; 64: 792-797.
• 14 Grimes J, Celler A, Birkenfeld B. et al. Patient-specific radiation dosimetry of ^99mTc-HYNIC-Tyr3-octreotide in neuroendocrine tumors. J Nucl Med 2011; 52: 1474-1481.
• 15 Guggenberg EV, Mikolajczak R, Janota B. et al. Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide, a somatostatin analog for tumor diagnosis. J Pharm Sci 2004; 93: 2497-2506.
• 16 Hartmann H, Zöphel K, Freudenberg R. et al. Strahlenexposition der Patienten bei Untersuchungen mit ⁶⁸Ga-DOTATOC am PET/CT. Nuklearmedizin 2009; 48: 201-207.
• 17 Hofmann M, Maecke H, Börner A. et al. Biokinetics and imaging with the somatostatin receptor PET radioligand ⁶⁸Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001; 28: 1751-1757.
• 18 Jimenez Londono GA, Garcia Vicente AM, Soriano Castrejon AM. et al. Role of ^99mTc-HYNIC-Tyr3-octreotide scintigraphy in neuroendocrine tumors based on localization of the primary tumor. Minerva Endocrinol 2016; 41: 10-18.
• 19 Krausz Y, Freedman N, Rubinstein R. et al. ⁶⁸Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with ^mIn-DTPA-octreotide (OctreoScan®). Mol Imaging Biol 2011; 13: 583-593.
• 20 Krenning EP, Bakker WH, Kooij PP. et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 1992; 33: 652-658.
• 21 Krenning EP, Kwekkeboom DJ, Bakker WH. et al. Somatostatin receptor scintigraphy with [¹¹¹In-DTPA-D-Phe1]-and [¹²³I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20: 716-731.
• 22 Li X, Bauer W, Kreissl MC. et al. Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice. Atherosclerosis 2013; 230: 33-39.
• 23 Madrzak D, Mikolajczak R, Kaminski G. Influence of PET/CT Ga-68 somatostatin receptor imaging on proceeding with patients, who were previously diagnosed with Tc-99m-EDDA/HYNIC-TOC SPECT. Nucl Med Rev 2016; 19: 88-92.
• 24 Modlin IM, Kidd M, Latich I. et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751.
• 25 Modlin IM, Oberg K, Chung DC. et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008; 9: 61-72.
• 26 Naswa N, Sharma P, Kumar A. et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. Am J of Roentgenol 2011; 197: 1221-1228.
• 27 O’Connor MK, Kemp BJ. Single-photon emission computed tomography/computed tomography: basic instrumentation and innovations. Semin Nucl Med 2006; 36: 258-266.
• 28 Perri M, Erba P, Volterrani D. et al. Octreo-SPECT/ CT imaging for accurate detection and localization of suspected neuroendocrine tumors. Q J Nucl Med Mol Imaging 2008; 52: 323-333.
• 29 Qiao Z, Zhang J, Jin X. et al. ^99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors. Clin Nucl Med 2015; 40: 397-400.
• 30 Sainz-Esteban A, Olmos R, Gonzalez-Sagrado M. et al. Contribution of ¹¹¹In-pentetreotide SPECT/ CT imaging to conventional somatostatin receptor scintigraphy in the detection of neuroendocrine tumours. Nucl Med Commun 2015; 36: 251-259.
• 31 Sepulveda-Mendez J, de Murphy CA, Pedraza-Lopez M. et al. Specificity and sensitivity of (99)mTc-EDDA/HYNIC-Tyr(3)-octreotide ((99)mTc-TOC) for imaging neuroendocrine tumors. Nucl Med Commun 2012; 33: 69-79.
• 32 Sergieva S, Robev B, Dimcheva M. et al. Clinical application of SPECT-CT with ^99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs). Nucl Med Rev 2016; 19: 81-87.
• 33 Sharma P, Sharma S, Ballal S. et al. SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone. Nucl Med Commun 2012; 33: 926-932.
• 34 Shi W, Johnston CF, Buchanan KD. et al. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. QJM 1998; 91: 295-301.
• 35 Sundin A, Garske U, Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007; 21: 69-85.
• 36 Taal BG, Visser O. Epidemiology of neuroendocrine tumours. Neuroendocrinology 2004; 80: 3-7.
• 37 Wang L, Yin X, Wang F. et al. The usefulness of combined diagnostic CT and (99m)Tc-octreotide somatostatin receptor SPECT/CT imaging on pulmonary nodule characterization in patients. Cancer Biother Radiopharmaceut 2013; 28: 731-736.
• 38 Wang S, Yang W, Deng J. et al. Correlation between ^99mTc-HYNIC-octreotide SPECT/CT somatostatin receptor scintigraphy and pathological grading of meningioma. J Neurooncol 2013; 113: 519-526.
• 39 Yamaga LY, Neto GC, da Cunha ML. et al. ^99mTc-HYNIC-TOC increased uptake can mimic malignancy in the pancreas uncinate process at somatostatin receptor SPECT/CT. Radiol Med 2016; 121: 225-228.
• 40 Zhao R, Wang J, Deng J. et al. Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves’ ophthalmopathy. Am J Nuc Med Mol Imag 2012; 2: 242-247.