Molecular imaging with ⁶⁸Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours

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 semiquantitative 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 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 (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 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.