Molecular Imaging with ⁶⁸Ga-SSTR PET/CT and Correlation to Immunohistochemistry of Somatostatin Receptors in Neuroendocrine Tumours

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2011 Jun 1

PMID 21626438

Citations 53

Authors

Daniel Kaemmerer

Luisa Peter

Amelie Lupp

Stefan Schulz

Jorg Sanger

Vikas Prasad

Harshad Kulkarni

Sven-Petter Haugvik

Merten Hommann

Richard Paul Baum

Affiliations

Soon will be listed here.

Abstract

Purpose: Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3-5.

Methods: Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative (68)Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUV(max) and SUV(mean)) were used for PET/CT.

Results: The IRS for SSTR2A and SSTR5 correlated highly significant with the SUV(max) on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUV(mean) (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading.

Conclusion: The highly significant correlation between SSTR2A and SSTR5 and the SUV(max) on the (68)Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of (68)Ga-DOTA-NOC to the SSTR subtypes and demonstrates the excellent qualification of somatostatin analogues in the diagnostics of NET. This study correlating somatostatin receptor imaging using (68)Ga-DOTA-NOC PET/CT with immunohistochemically analysed SSTR also underlines the approval of therapy using somatostatin analogues, follow-up imaging as well as radionuclide therapy.

Citing Articles

Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors.

Kim J, Kim J, Kim Y, Yang D, Yoo C, Park I Sci Rep. 2024; 14(1):4047.

PMID: 38374188 PMC: 10876978. DOI: 10.1038/s41598-024-54599-4.

Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer.

Wang H, Remke M, Horn T, Schwamborn K, Chen Y, Steiger K EJNMMI Res. 2023; 13(1):99.

PMID: 37971546 PMC: 10654338. DOI: 10.1186/s13550-023-01044-8.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

Fabritius M, Soltani V, Cyran C, Ricke J, Bartenstein P, Auernhammer C Cancer Imaging. 2023; 23(1):92.

PMID: 37770958 PMC: 10537814. DOI: 10.1186/s40644-023-00614-2.

A prospective head-to-head comparison of [Ga]Ga-P16-093 and [Ga]Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

Wang G, Li L, Zhu M, Zang J, Wang J, Wang R Eur J Nucl Med Mol Imaging. 2023; 50(10):3126-3136.

PMID: 37233785 PMC: 10213584. DOI: 10.1007/s00259-023-06283-4.

Neuroendocrine Tumors: Genomics and Molecular Biomarkers with a Focus on Metastatic Disease.

Alexander E, Ziv E Cancers (Basel). 2023; 15(8).

PMID: 37190177 PMC: 10137277. DOI: 10.3390/cancers15082249.

References

Miederer M, Seidl S, Buck A, Scheidhauer K, Wester H, Schwaiger M . Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging. 2008; 36(1):48-52. DOI: 10.1007/s00259-008-0944-5. View

Zamora V, Cabanne A, Salanova R, Bestani C, Domenichini E, Marmissolle F . Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours. Dig Liver Dis. 2009; 42(3):220-5. DOI: 10.1016/j.dld.2009.07.018. View

Reubi J . Somatostatin and other Peptide receptors as tools for tumor diagnosis and treatment. Neuroendocrinology. 2004; 80 Suppl 1:51-6. DOI: 10.1159/000080742. View

Antunes P, Ginj M, Zhang H, Waser B, Baum R, Reubi J . Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?. Eur J Nucl Med Mol Imaging. 2007; 34(7):982-93. DOI: 10.1007/s00259-006-0317-x. View

Kulaksiz H, Eissele R, Rossler D, Schulz S, Hollt V, Cetin Y . Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtype specific antibodies. Gut. 2002; 50(1):52-60. PMC: 1773091. DOI: 10.1136/gut.50.1.52. View

Wild D, Schmitt J, Ginj M, Macke H, Bernard B, Krenning E . DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging. 2003; 30(10):1338-47. DOI: 10.1007/s00259-003-1255-5. View

Reubi J, Waser B, Schaer J, Laissue J . Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001; 28(7):836-46. DOI: 10.1007/s002590100541. View

Buscail L, Saint-Laurent N, Chastre E, Vaillant J, Gespach C, Capella G . Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer. Cancer Res. 1996; 56(8):1823-7. View

Reubi J, Laissue J, Waser B, Horisberger U, Schaer J . Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann N Y Acad Sci. 1994; 733:122-37. DOI: 10.1111/j.1749-6632.1994.tb17262.x. View

10.

Reubi J . Peptide receptor expression in GEP-NET. Virchows Arch. 2007; 451 Suppl 1:S47-50. DOI: 10.1007/s00428-007-0443-2. View

11.

Reubi J . Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003; 24(4):389-427. DOI: 10.1210/er.2002-0007. View

12.

Rufini V, Calcagni M, Baum R . Imaging of neuroendocrine tumors. Semin Nucl Med. 2006; 36(3):228-47. DOI: 10.1053/j.semnuclmed.2006.03.007. View

13.

Reubi J, Krenning E, Lamberts S, Kvols L . Somatostatin receptors in malignant tissues. J Steroid Biochem Mol Biol. 1990; 37(6):1073-7. DOI: 10.1016/0960-0760(90)90468-z. View

14.

Reubi J, Schaer J, Waser B, Mengod G . Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Res. 1994; 54(13):3455-9. View

15.

Schulz S, Schmitt J, Wiborny D, Schmidt H, Olbricht S, Weise W . Immunocytochemical detection of somatostatin receptors sst1, sst2A, sst2B, and sst3 in paraffin-embedded breast cancer tissue using subtype-specific antibodies. Clin Cancer Res. 1998; 4(9):2047-52. View

16.

Thodou E, Kontogeorgos G, Theodossiou D, Pateraki M . Mapping of somatostatin receptor types in GH or/and PRL producing pituitary adenomas. J Clin Pathol. 2006; 59(3):274-9. PMC: 1860351. DOI: 10.1136/jcp.2005.026914. View

17.

Reubi J, Waser B, van Hagen M, Lamberts S, Krenning E, Gebbers J . In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas. Int J Cancer. 1992; 50(6):895-900. DOI: 10.1002/ijc.2910500613. View

18.

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(11):4519-24. DOI: 10.1210/jc.2008-1063. View

19.

Schulz S, Schreff M, Schmidt H, Handel M, Przewlocki R, Hollt V . Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia. Eur J Neurosci. 1999; 10(12):3700-8. DOI: 10.1046/j.1460-9568.1998.00386.x. View

20.

Reubi J, Schar J, Waser B, Wenger S, Heppeler A, Schmitt J . Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000; 27(3):273-82. DOI: 10.1007/s002590050034. View