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

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.