Imaging Properties and Tumor Targeting of <sup>68</sup>Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients

oleh: Leonhard Gruber, Clemens Decristoforo, Christian Uprimny, Peter Hohenberger, Stefan O. Schoenberg, Francesca Orlandi, Maurizio Franco Mariani, Claudia Manzl, Maria Theresia Kasseroler, Herbert Tilg, Bettina Zelger, Werner R. Jaschke, Irene J. Virgolini

Format: Article
Diterbitkan: MDPI AG 2022-11-01

Deskripsi

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a <sup>68</sup>Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of <sup>68</sup>Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based <sup>68</sup>Ga-NeoBOMB1 preparation with a licensed <sup>68</sup>Ge/<sup>68</sup>Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3–4 h post injection (first six patients) and static PET scans 2 and 3–4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant <sup>68</sup>Ga-NeoBOMB1 uptake (median SUV<sub>max</sub> 11.8 [range 2.8–51.1] 2 h p.i. and 13.2 [range 2.5–53.8] 3–4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by <sup>68</sup>Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (<i>p</i> < 0.0001), higher body mass index (<i>p</i> = 0.007), and non-necrotic lesion appearance (<i>p</i> = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: <sup>68</sup>Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.