Correlation of Somatostatin Receptor 1-5 Expression, [68Ga]Ga-DOTANOC, [18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms

Susanna Majala; Tiina Vesterinen; Hanna Seppänen; Harri Mustonen; Jari Sundström; Camilla Schalin-Jäntti; Risto Gullichsen; Jukka Schildt; Jukka Kemppainen; Johanna Arola; Saila Kauhanen

doi:10.3390/cancers14010162

Correlation of Somatostatin Receptor 1-5 Expression, [⁶⁸Ga]Ga-DOTANOC, [¹⁸F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms

Cancers (Basel). 2021 Dec 29;14(1):162. doi: 10.3390/cancers14010162.

Authors

Susanna Majala^{1

2}, Tiina Vesterinen^{3

4}, Hanna Seppänen⁵, Harri Mustonen⁵, Jari Sundström⁶, Camilla Schalin-Jäntti⁷, Risto Gullichsen¹, Jukka Schildt⁸, Jukka Kemppainen^{2

9}, Johanna Arola³, Saila Kauhanen^{1

2}

Affiliations

¹ Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland.
² Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland.
³ HUSLAB, HUS Diagnostic Center, Department of Pathology, Helsinki University Hospital, University of Helsinki, P.O. Box 400, FIN-00029 Helsinki, Finland.
⁴ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, P.O. Box 20, FIN-00014 Helsinki, Finland.
⁵ Translational Cancer Medicine Research Program, Department of Surgery, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland.
⁶ Department of Pathology, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland.
⁷ Abdominal Center, Division of Endocrinology, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland.
⁸ Department of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, FIN-00029 Helsinki, Finland.
⁹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland.

Abstract

Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [⁶⁸Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs.

Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [⁶⁸Ga]Ga-DOTANOC and [¹⁸F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [⁶⁸Ga]Ga-DOTANOC and [¹⁸F]F-FDG PET/CT.

Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [⁶⁸Ga]Ga-DOTANOC finding (Spearman's rho 0.382, p = 0.043). All [⁶⁸Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (-0.353, 95% CI -0.654-0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0-3.0) and 6.38 (SD 7.25, CI 2.25-8.75) for negative tumors.

Conclusion: SSTR2 was the only SSTR subtype to correlate with [⁶⁸Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.

Keywords: immunohistochemistry; non-functional pancreatic neuroendocrine neoplasm; positron emission tomography; prospective study; somatostatin receptors; surgical management.

Abstract

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