title: Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT).
  
  
  METHODS
  Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients.
  
  
  RESULTS
  Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05).
  
  
  CONCLUSIONS
  Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
authors.affiliation: Department of Pathology, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Arne
authors.forename: Bengt
authors.initials: B
authors.lastname: Nilsson
authors.forename: Johanna
authors.initials: J
authors.lastname: Dalmo
authors.forename: Erik
authors.initials: E
authors.lastname: Kristiansson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Arvidsson
authors.forename: Eva
authors.initials: E
authors.lastname: Forssell-Aronsson
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007553:Isotope Labeling; D008187:Lutetium / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C094279:indium-111-octreotide; D013004:Somatostatin; D008187:Lutetium; D015282:Octreotide