Horm Metab Res 2010; 42(8): 599-606
DOI: 10.1055/s-0030-1253354
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Association of Somatostatin Receptor 2 Immunohistochemical Expression with [111In]-DTPA Octreotide Scintigraphy and [68Ga]-DOTATOC PET/CT in Neuroendocrine Tumors

K. Müssig1 , M. Ö. Öksüz2 , K. Dudziak1 , B. Ueberberg3 , M. Wehrmann4 , M. Horger5 , S. Schulz6 , H.U. Häring1 , C. Pfannenberg5 , R. Bares2 , B. Gallwitz1 , S. Petersenn3
  • 1Division of Endocrinology, Diabetes, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, University Hospital of Tübingen, Tübingen, Germany
  • 2Department of Nuclear Medicine, University Hospital of Tübingen, Tübingen, Germany
  • 3Division of Endocrinology, Medical Center, University of Duisburg-Essen, Essen, Germany
  • 4Department of Pathology, University Hospital of Tübingen, Tübingen, Germany
  • 5Department of Radiology, University Hospital of Tübingen, Tübingen, Germany
  • 6Department of Pharmacology and Toxicology, Friedrich-Schiller-University, Jena, Germany
Further Information

Publication History

received 27.11.2009

accepted 24.03.2010

Publication Date:
26 April 2010 (online)

Abstract

In the absence of preoperative somatostatin receptor (sst) scans, knowledge of immunohistochemical sst2 tumor expression may help predicting the success of somatostatin analogue-based follow-up studies and treatment of neuroendocrine tumors (NET). We studied the association between sst immunostaining and tracer uptake in [111In]-DTPA octreotide (DTPAOC) scintigraphy and [68Ga]-DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET)/computed tomography (CT). Retrospective analy-sis of 36 NET patients was carried out. In 40 tumors, immunohistochemical sst2, sst3, and sst5 expressions were analyzed using a pathological scoring, applying monoclonal (sst2) or polyclonal antibodies (sst3, sst5). In 14 lesions, [111In]-DTPAOC uptake was assessed by a semiquantitative score. In 26 tumors, [68Ga]-DOTATOC PET/CT was quantified using an uptake score and maximal standard uptake value (SUVmax). Combined and separate qualitative analysis of sst scans revealed significant associations between increased tracer uptake and immunohistochemical sst2 detection (combined: ρ=0.56, p=0.0002, [111In]-DTPAOC: ρ=0.63, p=0.0152, and [68Ga]-DOTATOC: ρ=0.52, p=0.0065, respectively). In contrast, sst3 and sst5 immunostaining was not associated with tracer uptake (all p>0.14). The semiquantitative immunohistochemical score for sst2 was associated with the [68Ga]-DOTATOC uptake score and SUVmax values (ρ=0.67, p=0.0002 and ρ=0.63, p=0.0010, respectively), but not with the [111In]-DTPAOC uptake score (ρ=0.24, p=0.4). In patients without preoperative sst scans, knowledge of immunohistochemical sst2 expression may help estimating the value of sst imaging in the clinical follow-up, in particular in those lesions with positive sst2 immunostaining. Negativity for sst2, however, does not rule out tracer uptake in some patients, with heterogeneous sst2 expression within the tumor as a potential explanation.

References

  • 1 Kulaksiz H, Eissele R, Rossler D, Schulz S, Hollt V, Cetin Y, Arnold R. Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies.  Gut. 2002;  50 52-60
  • 2 Slooter GD, Mearadji A, Breeman WA, Marquet RL, de Jong M, Krenning EP, van Eijck CH. Somatostatin receptor imaging, therapy and new strategies in patients with neuroendocrine tumours.  Br J Surg. 2001;  88 31-40
  • 3 Gibril F, Reynolds JC, Doppman JL, Chen CC, Venzon DJ, Termanini B, Weber HC, Stewart CA, Jensen RT. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study.  Ann Intern Med. 1996;  125 26-34
  • 4 Shi W, Johnston CF, Buchanan KD, Ferguson WR, Laird JD, Crothers JG, McIlrath EM. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging.  QJM. 1998;  91 295-301
  • 5 Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schäfer M, Schilling T, Haufe S, Herrmann T, Haberkorn U. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours.  Eur J Nucl Med Mol Imaging. 2007;  34 1617-1626
  • 6 Koukouraki S, Strauss LG, Georgoulias V, Schuhmacher J, Haberkorn U, Karkavitsas N, Dimitrakopoulou-Strauss A. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.  Eur J Nucl Med Mol Imaging. 2006;  33 460-466
  • 7 Kwekkeboom DJ, Kooij PP, Bakker WH, Macke HR, Krenning EP. Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake.  J Nucl Med. 1999;  40 762-767
  • 8 Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, Bartolomei M, Orsi F, De Cicco C, Mäcke HR, Chinol M, de Braud F. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide.  Eur J Nucl Med. 2001;  28 426-434
  • 9 Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-d-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumors: a clinical phase II study.  Ann Oncol. 2001;  12 941-945
  • 10 Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours.  Lancet Oncol. 2008;  9 61-72
  • 11 Unger N, Serdiuk I, Sheu SY, Walz MK, Schulz S, Saeger W, Schmid KW, Mann K, Petersenn S. Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumors.  Clin Endocrinol (Oxf). 2008;  68 850-857
  • 12 Fischer T, Doll C, Jacobs S, Kolodziej A, Stumm R, Schulz S. Reassessment of sst2 somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-1.  J Clin Endocrinol Metab. 2008;  93 4519-4524
  • 13 Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, Jahn M, Jennewein M, Rösch F. Processing of generator-produced 68Ga for medical application.  J Nucl Med. 2007;  48 1741-1748
  • 14 Dimitroulopoulos D, Xynopoulos D, Tsamakidis K, Paraskevas E, Zisimopoulos A, Andriotis E, Fotopoulou E, Kontis M, Paraskevas I. Scintigraphic detection of carcinoid tumors with a cost effectiveness analysis.  World J Gastroenterol. 2004;  10 3628-3633
  • 15 Cimitan M, Buonadonna A, Cannizzaro R, Canzonieri V, Borsatti E, Ruffo R, De Apollonia L. Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role.  Ann Oncol. 2003;  14 1135-1141
  • 16 Volante M, Brizzi MP, Faggiano A, La Rosa S, Rapa I, Ferrero A, Mansueto G, Righi L, Garancini S, Capella C, De Rosa G, Dogliotti L, Colao A, Papotti M. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy.  Mod Pathol. 2007;  20 1172-1182
  • 17 Asnacios A, Courbon F, Rochaix P, Bauvin E, Cances-Lauwers V, Susini C, Schulz S, Boneu A, Guimbaud R, Buscail L. Indium-111-pentetreotide scintigraphy and somatostatin receptor subtype 2 expression: new prognostic factors for malignant well-differentiated endocrine tumors.  J Clin Oncol. 2008;  26 963-970
  • 18 Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, Perren A. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in (68)Ga-DOTATOC PET/CT.  Eur J Nucl Med Mol Imaging. 2009;  36 48-52
  • 19 Ueberberg B, Tourne H, Redman A, Walz MK, Schmid KW, Mann K, Petersenn S. Differential expression of the human somatostatin receptor subtypes sst1 to sst5 in various adrenal tumors and normal adrenal gland.  Horm Metab Res. 2005;  37 722-728
  • 20 Tulipano G, Schulz S. Novel insights in somatostatin receptor physiology.  Eur J Endocrinol. 2007;  156 (S 01) S3-S11

Correspondence

PD Dr. K. MüssigMD 

Medizinische Klinik IV

Universitätsklinikum Tübingen

Otfried-Müller-Straße 10

72076 Tübingen

Germany

Phone: +49 7071 29 83670

Fax: +49 7071 29 2784

Email: Karsten.Muessig@med.uni-tuebingen.de

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