(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2

Ingrid H Olsen; Seppo W Langer; Birgitte H Federspiel; Jytte Oxbøl; Annika Loft; Anne Kiil Berthelsen; Jann Mortensen; Peter Oturai; Ulrich Knigge; Andreas Kjær

(68)Ga-DOTATOC PET and gene expression profile in patients with neuroendocrine carcinomas: strong correlation between PET tracer uptake and gene expression of somatostatin receptor subtype 2

Am J Nucl Med Mol Imaging. 2016 Jan 28;6(1):59-72. eCollection 2016.

Authors

Affiliations

¹ European NET Centre of Excellence, Rigshospitalet, University of CopenhagenDenmark; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of CopenhagenDenmark; Department of Endocrinology, Rigshospitalet, University of CopenhagenDenmark; Department of Surgical Gastroenterology, Rigshospitalet, University of CopenhagenDenmark; Department of Oncology, Rigshospitalet, University of CopenhagenDenmark; Department of Pathology, Rigshospitalet, University of CopenhagenDenmark.
² European NET Centre of Excellence, Rigshospitalet, University of CopenhagenDenmark; Department of Oncology, Rigshospitalet, University of CopenhagenDenmark.
³ European NET Centre of Excellence, Rigshospitalet, University of CopenhagenDenmark; Department of Pathology, Rigshospitalet, University of CopenhagenDenmark.
⁴ European NET Centre of Excellence, Rigshospitalet, University of CopenhagenDenmark; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of CopenhagenDenmark.
⁵ European NET Centre of Excellence, Rigshospitalet, University of CopenhagenDenmark; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of CopenhagenDenmark; Department of Endocrinology, Rigshospitalet, University of CopenhagenDenmark; Department of Surgical Gastroenterology, Rigshospitalet, University of CopenhagenDenmark.

PMID: 27069766
PMCID: PMC4749505

Abstract

Somatostatin receptor expression on both protein and gene expression level was compared with in vivo (68)Ga-DOTATOC PET/CT in patients with neuroendocrine carcinomas (NEC). Twenty-one patients with verified NEC who underwent a (68)Ga-DOTATOC PET/CT between November 2012 and May 2014, were retrospectively included. By real-time polymerase chain reaction, we quantitatively determined the gene expression of several genes and compared with (68)Ga-DOTATOC PET uptake. By immunohistochemistry we qualitatively studied the expression of assorted proteins in NEC. The median age at diagnosis was 68 years (range 41-84) years. All patients had WHO performance status 0-1. Median Ki67 index was 50% (range 20-100%). Gene expression of somatostatin receptor subtype (SSTR) 2 and Ki67 were both positively correlated to the (68)Ga-DOTATOC uptake (r=0.89; p<0.0001 and r=0.5; p=0.021, respectively). Furthermore, SSTR2 and SSTR5 gene expression were strongly and positively correlated (r=0.57; p=0.006). This study as the first verifies a positive and close correlation of (68)Ga-DOTATOC uptake and gene expression of SSTR2 in NEC. SSTR2 gene expression has a stronger correlation to (68)Ga-DOTATOC uptake than SSTR5. In addition, the results indicate that the gene expression levels of SSTR2 and SSTR5 at large follow one another.

Keywords: 68Ga-DOTATOC PET/CT; Neuroendocrine carcinoma; gene expression; imaging; immunohistochemistry; mammalian target of rapamycin; neuroendocrine tumors; somatostatin receptor type 2; somatostatin receptor type 5; urokinase-type plasminogen activator receptor.