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

Abstract

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-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 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga 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 68Ga-NeoBOMB1 uptake (median SUVmax 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 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-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.

Peptide Radioligands in Cancer Theranostics: Agonists and Antagonists

“…In line with this, multiple mediastinal, abdominal, paraesophageal, and pelvic lymph node metastases were successfully visualized in a prostate adenocarcinoma patient, following postradical prostatovesiculectomy with pelvic lymphadenectomy, intensity-modulated radiotherapy, and androgen-deprivation therapy on [ 68 Ga]Ga-NeoBOMB1 PET/CT, as shown in Figure 8. Similar findings were obtained from a following phase I/IIa clinical trial (EudraCT 2016-002053-38) in nine patients with advanced GIST, with a representative ileal GIST patient showing strong uptake of [ 68 Ga]Ga-NeoBOMB1 in hepatic metastases on PET/CT [117,118]. The tracer demonstrated excellent safety profile, low radiation dose, high metabolic stability and apparent suitability for PET diagnostic imaging of GRPR expression in oncologic patients.…”

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

“…To overcome these challenges and enhance the efficacy of GRPR-targeted radiotracers, recent research endeavors have shifted their focus towards antagonist molecules. The two most promising radiopharmaceuticals, 68 Ga-RM2 and 68 Ga-NeoB, have been successfully evaluated for the ability to bind GRPR-expressing tumors with high sensitivity [130][131][132][133][134].…”

Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives

“…A phase I/IIa trial evaluated the role of 68Ga-labelled antagonists to GRPRs as radioligands for nuclear imaging in GISTs. 68Ga-NeoBOMB1-PET showed variable uptakes in advanced-GISTs, resulting in a possible new diagnostic option in selected cases [ 134 ]. Currently, a phase I/IIa trial is testing 177Lu-NeoB to confirm its potential as a theragnostic agent in adult patients with advanced solid tumors with an overexpression of GRPR (NCT03872778).…”