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Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.

Gabriella Arne ; Bengt E Nilsson ; Johanna Dalmo ; Erik Kristiansson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Yvonne Arvidsson ; Eva Forssell-Aronsson ; Ola Nilsson ; Håkan Ahlman
Acta oncologica (Stockholm, Sweden) (1651-226X). Vol. 52 (2013), 4, p. 783-792.
[Artikel, refereegranskad vetenskaplig]

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). Material and 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). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.



Denna post skapades 2012-12-14. Senast ändrad 2015-03-12.
CPL Pubid: 167832

 

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Institutioner (Chalmers)

Institutionen för biomedicin, avdelningen för patologi (GU)
Institutionen för kliniska vetenskaper, sektionen för kirurgi och kirurgisk gastroforskning, Avdelningen för kirurgi (GU)
Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik (GU)
Sahlgrenska Cancer Center (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)

Ämnesområden

Cancer och onkologi
Radiofysik
Kirurgi

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