Background <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Clinical trial number <p>Not applicable.</p>