title: Molecular imaging with ⁶⁸Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General and Visceral Surgery, Zentralklinik Bad Berka GmbH, Robert-Koch-Allee 9, 99437 Bad Berka, Germany. Daniel.Kaemmerer@zentralklinik.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaemmerer
authors.forename: Luisa
authors.initials: L
authors.lastname: Peter
authors.forename: Amelie
authors.initials: A
authors.lastname: Lupp
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.forename: Vikas
authors.initials: V
authors.lastname: Prasad
authors.forename: Harshad
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Sven-Petter
authors.initials: SP
authors.lastname: Haugvik
authors.forename: Merten
authors.initials: M
authors.lastname: Hommann
authors.forename: Richard Paul
authors.initials: RP
authors.lastname: Baum
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001692:Biological Transport; D053379:Chromogranin A / Q000378:metabolism; D005710:Gallium Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019394:Ki-67 Antigen / Q000378:metabolism; D057054:Molecular Imaging; D064847:Multimodal Imaging; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D049268:Positron-Emission Tomography; D017481:Receptors, Somatostatin / Q000276:immunology / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016708:Synaptophysin / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D053379:Chromogranin A; D005710:Gallium Radioisotopes; D019394:Ki-67 Antigen; D017481:Receptors, Somatostatin; D016708:Synaptophysin