RSS-Feed abonnieren
DOI: 10.1055/s-0030-1253354
© 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
Publikationsverlauf
received 27.11.2009
accepted 24.03.2010
Publikationsdatum:
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.
Key words
neuroendocrine tumors - NET - sst - [68Ga]-DOTA-Tyr-octreotide - [111In]-DTPAOC
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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 20
Tulipano G, Schulz S.
Novel insights in somatostatin receptor physiology.
Eur J Endocrinol.
2007;
156
(S 01)
S3-S11
MissingFormLabel
Correspondence
PD Dr. K. MüssigMD
Medizinische Klinik IV
Universitätsklinikum Tübingen
Otfried-Müller-Straße 10
72076 Tübingen
Germany
Telefon: +49 7071 29 83670
Fax: +49 7071 29 2784
eMail: Karsten.Muessig@med.uni-tuebingen.de