Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours
- 732 Downloads
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.
Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative 68Ga-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 (SUVmax and SUVmean) were used for PET/CT.
The IRS for SSTR2A and SSTR5 correlated highly significant with the SUVmax on the PET/CT (p < 0.001; p < 0.05) and the IRS for SSTR2A with the SUVmean (p < 0.013). The level of SSTR2A score correlated significantly with chromogranin A staining and indirectly to the tumour grading.
The highly significant correlation between SSTR2A and SSTR5 and the SUVmax on the 68Ga-DOTA-NOC PET/CT scans is concordant with the affinity profile of 68Ga-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 68Ga-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.
KeywordsNeuroendocrine tumour Somatostatin receptor imaging Somatostatin receptor immunohistochemistry Clone UMB-1
Each author has contributed significantly to the submitted work. Daniel Kaemmerer had the conception, designed and performed the study and surgery, collected the tumours and drafted the manuscript. Luisa Peter performed the study, analysed, interpreted the data and wrote the manuscript. Sven-Petter Haugvik operated on the patients, critically contributed and revised the manuscript. Amelie Lupp developed the antibodies, contributed to the conception and to acquiring the data. Stefan Schulz developed the antibodies, critically revised and approved the final manuscript. Jörg Sänger analysed and interpreted the data and enhanced the intellectual content. Vikas Prasad contributed to the conception, performed the PET/CT imaging and analysed the data. Harshad Kulkarni revised and approved the final manuscript. Richard Paul Baum contributed to the conception, performed the PET/CT imaging and critically revised and approved the final manuscript. Merten Hommann performed the surgery, collected the tumours and critically revised and approved the final manuscript.
Conflicts of interest
- 15.Papotti M, Bongiovanni M, Volante M, Allia E, Landolfi S, Helboe L, et al. Expression of somatostatin receptor types 1–5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch 2002;440:461–75.PubMedCrossRefGoogle Scholar