High expression of peptide receptors as a novel target in gastrointestinal stromal tumours

  • Jean Claude ReubiEmail author
  • Meike Körner
  • Beatrice Waser
  • Luca Mazzucchelli
  • Louis Guillou
Original Article


Recent significant advances in understanding the biology of gastrointestinal stromal tumours (GIST) have led to the introduction of a new targeted therapy (imatinib mesylate, Glivec). Hopes of a new era of a specific cancer therapy, however, have been tempered by the recognition that a significant proportion of patients who initially respond to the drug eventually become resistant to it. Given the successful development of peptide receptor scintigraphy and radiotherapy for neuroendocrine tumours, we postulated that a similar approach could offer a valid alternative in the diagnosis and therapy of GIST. Using in vitro receptor autoradiography to measure peptide receptors, we found that 16/19 GIST expressed bombesin subtype 2 receptors, 16/19 expressed vasoactive intestinal peptide subtype 2 receptors (VPAC2) and 12/19 expressed cholecystokinin subtype 2 receptors, in most cases in extremely high densities. All GIST metastases were shown to express two or more of these peptide receptors in very high density. Receptors were also expressed in non-responders to Glivec or after chemo-embolisation. Conversely, somatostatin subtype 2, cholecystokinin subtype 1, bombesin subtype 1 and 3, and neuropeptide Y subtype Y1 and Y2 receptors were not or only rarely expressed. These data represent a strong molecular basis for the use of radiolabelled bombesin, vasoactive intestinal peptide and/or cholecystokinin analogues as targeting agents to localise GIST tumours in patients by in vivo scintigraphy and/or to perform targeted radiotherapy to destroy GIST primaries, metastases and recurrences, including those resistant to Glivec.


Gastrointestinal stromal tumours Cancer targeting Peptide receptors Bombesin receptors Cholecystokinin receptors 



We thank Dr. P. Robberecht, Brussels, for the gift of Ro25-1553 and KRL-VIP/GRF. We also thank Mrs. R. Rehmann and V. Eltschinger, Berne, for excellent technical assistance, and Dr. Hanifa Bouzourene for her help in selecting the GIST cases.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jean Claude Reubi
    • 1
    Email author
  • Meike Körner
    • 1
  • Beatrice Waser
    • 1
  • Luca Mazzucchelli
    • 1
    • 2
  • Louis Guillou
    • 3
  1. 1.Division of Cell Biology and Experimental Cancer Research, Institute of PathologyUniversity of BerneBerneSwitzerland
  2. 2.Institute of PathologyLocarnoSwitzerland
  3. 3.Institute of PathologyUniversity of LausanneLausanneSwitzerland

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