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In vivo gastrin releasing peptide receptor expression in SDH deficient wild-type gastrointestinal stromal tumours (GIST): potential for theranostic applications

  • David G. E. Hulse
  • , Ines Harper
  • , Fung Tan
  • , Daniel Gillett
  • , Victoria Warnes
  • , Mary McLean
  • , Pascal Wodtke
  • , Ferdia Gallagher
  • , Eamonn R Maher
  • , Olivier Giger
  • , Ramesh Bulusu
  • , Luigi Aloj*
  • , Ruth T. Casey*
    • *Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Succinate dehydrogenase (SDH) deficient wild-type Gastrointestinal Stromal Tumours (wtGIST) are a rare GIST subtype with limited treatment options. Gallium-68 labelled Gastrin Releasing Peptide Receptor (GRPR) antagonist NeoB has shown promise in PET imaging for multiple primary malignancies. This investigation sought to assess the biodistribution of [68Ga]NeoB via PET/CT imaging in metastatic wtGIST patients and aimed to evaluate GRPR expression in lesions to determine the ligand’s potential for patient selection in future therapeutic trials. Results: Twelve patients with histologically confirmed metastatic wtGIST were enrolled. [68Ga]NeoB PET/CT imaging was conducted for lesion segmentation and analysis of uptake characteristics. 8 of 12 (66.7%) patients exhibited intense but heterogeneous [68Ga]NeoB uptake in lesions, with variable tracer uptake both within and between lesions. Physiological uptake was highest in the pancreas, liver, and spleen. Four patients (33.3%) displayed minimal or no uptake in tumour lesions. Conclusions: The majority of wtGIST patients in this small cohort show lesions with intense [68Ga]NeoB uptake. Heterogeneity of uptake indicates GRPR has highly variable inter- and intralesional expression. NeoB has potential for theranostic application in wtGIST, with limited effective standard of care treatments available. Ongoing trials are investigating the therapeutic use of [177Lu]NeoB in this setting. Clinical trial number: Not applicable.
Original languageEnglish
Article number132
Number of pages11
JournalEJNMMI research
Volume15
Early online date21 Oct 2025
DOIs
Publication statusPublished - 21 Oct 2025

Bibliographical note

© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Data Access Statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding

Advanced Accelerator Applications, a Novartis company, has providedfunding and supply of kits for radiopharmaceutical preparation of [68Ga]NeoB. This work was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and notnecessarily those of the NIHR or the Department of Health and Social Care. This work was supported by the Cancer Research UK Cambridge Experimental Cancer Medicine Centre, and Cancer Research UK Cambridge Centre [C9685/A25117].

Access to Document

  • In vivo gastrin releasing peptide receptor expression in SDH deficient wild-type gastrointestinal stromal tumours (GIST): potential for theranostic applications - Hulse et al 2025

    © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

    Final published version, 1.39 MBLicence: CC BY 4.0

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