Nuklearmedizin 2012; 51(03): 95-100
DOI: 10.3413/Nukmed-0428-11-08
Original article
Schattauer GmbH

Osseous metastases of gastro- entero - pancreatic neuroendocrine tumours

Diagnostic value of intra-therapeutic 177Lu-octreotate imaging in comparison with bone scintigraphyDetektion von Knochenmetastasen in Patienten mit gastroenteropankreatischen neuroendokrinen TumorenVergleich von Knochenszintigraphie und 177Lu-Octreotate-Scan
A. Sabet*
1   Nuclear Medicine, University Hospital Bonn, Germany
,
S. Ezziddin*
1   Nuclear Medicine, University Hospital Bonn, Germany
,
F. Heinemann
1   Nuclear Medicine, University Hospital Bonn, Germany
,
S. Guhlke
1   Nuclear Medicine, University Hospital Bonn, Germany
,
M. Muckle
1   Nuclear Medicine, University Hospital Bonn, Germany
,
W. Willinek
2   Radiology, University Hospital Bonn, Germany
,
H.-J. Biersack
1   Nuclear Medicine, University Hospital Bonn, Germany
,
H. Ahmadzadehfar
1   Nuclear Medicine, University Hospital Bonn, Germany
› Author Affiliations
Further Information

Publication History

received: 28 August 2011

accepted in revised form: 10 January 2012

Publication Date:
29 December 2017 (online)

Summary

Aim: Peptide receptor radionuclide therapy with 177Lu-octreotate is an effective treatment option for metastatic gastroenteropancreatic neuroendocrine tumors (GEP NET) and allows intratherapeutic imaging through a 177Lu-octreotate scan (LuS). The diagnostic value of this treatment scan is not yet established. This study aims to compare the sensitivity of LuS and bone scintigraphy (BS) regarding bone metastases and investigate potential implications of functional imaging results. Patients, methods: We retrospectively analyzed 29 consecutive GEP NET patients with bone metastases and baseline BS treated with 177Lu-octreotate. A semi-quantitative scoring system was used for the comparative evaluation. Treatment outcome (time-to-progression of bone metastases) was correlated with the intra-individual imaging discrepancy (Kaplan- Meyer curves, log-rank test, p < 0.05). Results: In 19 of 29 patients (65.5%) LuS was superior (LuS > BS), whereas in 10 patients (34.5%) both modalities were comparable. BS showed no additional (LuS-negative) metastatic bone lesions in our cohort. None of the investigated baseline characteristics was associated with Imaging discrepancy. On the other hand, functional imaging discrepancy had no impact on treatment response (p = 0.43) or time-to-progression (p = 0.92). Conclusions: Intra-therapeutic 177Lu-octreotate imaging is superior over bone scintigraphy for detection of bone metastases in GEP NET. BS may help to distinguish osseous from non-osseous localization. The presence of an osteoblastic correlate in BS seems to have no impact on therapeutic outcome

Zusammenfassung

Die Peptidrezeptor-Radionuklidtherapie (PRRT) mit 177Lu-Octreotate ist eine effektive Behandlungsoption für Patienten mit metastasierten gastroenteropankreatischen neuroendokrinen Tumoren (GEP-NET) und erlaubt eine intratherapeutische Bildgebung mittels 177Lu-Octreotate- Scan (LuS). Der diagnostische Wert dieses Scans ist bislang nicht definiert, unklar bleibt auch, ob eine zusätzliche osteometabole Bildgebung mittels konventioneller Knochenszintigraphie (BS) zur Komplettierung des Stagings bei Knochenmetastasen nötig ist. Ziel dieser Studie war es, Sensitivität von LuS und BS für Knochenmetastasen zu vergleichen und die imaging plikationen dieser bimodalen funktionellen Bildgebung zu untersuchen. Patienten, Methodik: Wir untersuchten retrospektiv eine konsekutive Kohorte von 29 GEP-NET-Patienten mit Knochenmetastasen, absolvierter PRRT mit 177Lu-octreotate und Basis-Knochenszintigraphie. Ein semiquantitatives Scoring- System wurde für die vergleichende Evaluation beider Modalitäten verwendet, der Einfluss verschiedener prätherapeutischer Tumorcharakteristika wie Plasma-CgA und -NSE-Spiegel, Ursprung des Primarius, Vortherapien sowie Tumorproliferationsrate wurde in diesem Zusammenhang untersucht, ebenfalls der Einfluss der intraindividuellen LuSBS- Diskrepanz auf das Langzeit-Behandlungsergebnis. Ergebnisse: In 19 von 29 Patienten (65,5%) war LuS dem BS überlegen, während in 10 Patienten (34,5%) beide Modalitäten eine vergleichbare Sensitivität hatten. BS zeigte keine zusätzlichen (LuS-negativen) Knochenmetastasen in unserer Studienkohorte. Kein Basischarakteristikum war mit einer Diskrepanz der zwei Modalitäten assoziiert. Eine Bildgebungsdiskrepanz wiederum war ohne Einfluss auf Behandlungserfolg (p = 0,43) oder progressionsfreie Zeit der Knochenmetastasen (p = 0,92). Schlussfolgerungen: Die intratherapeutische 177Lu-Octreotate Bildgebung ist der Knochenszintigraphie zum Nachweis von Knochenmetastasen bei GEPNET- Patienten, die sich einer PRRT unterziehen, überlegen. Dennoch kann die letztgenannte Modalität eine sinnvolle Ergänzung darstellen, um bei Metastasen die ossäre von der nicht ossären Lokalisation zu differenzieren und damit die Diagnose Knochenmetastasen sicher zu bestätigen. Eine osteoblastische Reaktion – dargestellt durch die Knochenszintigraphie – hatte in unserer Serie keinen Einfluss auf den Behandlungserfolg oder die Progressionsfreiheit der Knochenmetastasen.

* Both authors equally contributed to this work.


 
  • References

  • 1 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.
  • 2 Ambrosini V, Nanni C, Zompatori M. et al. 68Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2010; 37: 722-727.
  • 3 Breeman WA, De Jong M, Visser TJ. et al. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging 2003; 30: 917-920.
  • 4 Costelloe CM, Chuang HH, Madewell JE, Ueno NT. Cancer Response Criteria and Bone Metastases: RECIST 1.1, MDA and PERCIST. J Cancer 2010; 1: 80-92.
  • 5 Ezziddin S, Opitz M, Attassi M. et al. Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2011; 38: 459-466.
  • 6 Forrer F, Uusijarvi H, Storch D. et al. Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med 2005; 46: 1310-1316.
  • 7 Fukuoka M, Taki J, Mochizuki T, Kinuya S. Comparison of diagnostic value of 123I MIBG and high-dose 131I MIBG scintigraphy including incremental value of SPECT/CT over planar image in patients with malignant pheochromocytoma/paraganglioma and neuroblastoma. Clin Nucl Med 2011; 36: 1-7.
  • 8 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.
  • 9 Gibril F, Doppman JL, Reynolds JC. et al. Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect of their detection on management. J Clin Oncol 1998; 16: 1040-1053.
  • 10 Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992; 10: 239-253.
  • 11 Hoegerle S, Altehoefer C, Ghanem N. et al. Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology 2001; 220: 373-380.
  • 12 Jamar F, Fiasse R, Leners N, Pauwels S. Somatostatin receptor imaging with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors: safety, efficacy and impact on patient management. J Nucl Med 1995; 36: 542-549.
  • 13 Kwekkeboom DJ, Mueller-Brand J, Paganelli G. et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005; 46 (Suppl. 01) 62S-66S.
  • 14 Kwekkeboom DJ, de Herder WW, van Eijck CH. et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010; 40: 78-88.
  • 15 Lamberts SW, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 1990; 323: 1246-1249.
  • 16 Lebtahi R, Cadiot G, Delahaye N. et al. Detection of bone metastases in patients with endocrine gastroenteropancreatic tumors: bone scintigraphy compared with somatostatin receptor scintigraphy. J Nucl Med 1999; 40: 1602-1608.
  • 17 Meijer WG, van der Veer E, Jager PL. et al. Bone metastases in carcinoid tumors: clinical features, imaging characteristics, and markers of bone metabolism. J Nucl Med 2003; 44: 184-191.
  • 18 Panzuto F, Nasoni S, Falconi M. et al. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer 2005; 12: 1083-1092.
  • 19 Putzer D, Gabriel M, Henninger B. et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med 2009; 50: 1214-1221.
  • 20 Valkema R, Pauwels SA, Kvols LK. et al. Long-term follow-up of renal function after peptide receptor radiation therapy with 90Y-DOTA(0),Tyr(3)-octreotide and 177Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med 2005; 46 (Suppl. 01) 83S-91S.
  • 21 Van Essen M, Krenning EP, Kam BL. et al. Salvage therapy with 177Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med 2010; 51: 383-390.
  • 22 Versari A, Camellini L, Carlinfante G. et al. 68Ga DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study. Clin Nucl Med 2010; 35: 321-328.
  • 23 Zöphel K, Strumpf A, Wunderlich G. et al. Cure of neuroendocrine carcinoma by peptide receptor radionuclide therapy. Clin Nucl Med 2008; 33: 690-691.
  • 24 Zuetenhorst JM, Hoefnageli CA, Boot H. et al. Evaluation of 111In-pentetreotide, 131I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease. Nucl Med Commun 2002; 23: 735-741.