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

Eur J Nucl Med Mol Imaging. 2011 Sep;38(9):1659-68. doi: 10.1007/s00259-011-1846-5. Epub 2011 May 31.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Biological Transport
  • Chromogranin A / metabolism
  • Gallium Radioisotopes
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / diagnosis*
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / therapy
  • Ki-67 Antigen / metabolism
  • Molecular Imaging*
  • Multimodal Imaging*
  • Neoplasm Grading
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / therapy
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Positron-Emission Tomography*
  • Receptors, Somatostatin / immunology
  • Receptors, Somatostatin / metabolism*
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy
  • Synaptophysin / metabolism
  • Tomography, X-Ray Computed*

Substances

  • Antibodies, Monoclonal
  • Chromogranin A
  • Gallium Radioisotopes
  • Ki-67 Antigen
  • Receptors, Somatostatin
  • Synaptophysin

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor