Phase I study of [⁶⁸Ga]Ga-HX01 for targeting integrin αvβ3 and CD13 in healthy and malignancy subjects

Purpose: Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [⁶⁸Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.

Methods: This study enrolled 12 healthy volunteers (phase Ia) and 10 patients with malignant tumors (phase Ib). The subjects in phase Ia were divided into low-dose (0.05 mCi/kg) and high-dose (0.1 mCi/kg) groups. For phase Ia subjects, PET/CT images, blood and urine samples were collected to analyze the biodistribution, pharmacokinetics, radiation dosimetry, and safety of [⁶⁸Ga]Ga-HX01. For phase Ib patients, PET/MR scans were performed at 30 ± 5 and 60 ± 5 min after injection. The safety and preliminary diagnostic value of [⁶⁸Ga]Ga-HX01 were assessed.

Results: In phase Ia study, [⁶⁸Ga]Ga-HX01 was distributed and metabolized similarly in two dosage groups as the highest accumulations in kidneys and urine. It possessed quick renal excretion and blood clearance with an elimination half-life (T_1/2) of 28.92 ± 3.97 min. The total effective dose was 2.14 × 10^{- 2} mSv/MBq. In phase Ib study, [⁶⁸Ga]Ga-HX01 clearly detected the lesions per patient, and found a total of 59 lesions with varying uptake levels. For safety evaluation, no serious adverse events were observed during the examination.

Conclusion: [⁶⁸Ga]Ga-HX01 has proved to be a translational radiopharmaceutical with reliable security, favorable pharmacokinetics, and the ability to visualize tumors. The preliminary results in malignancy patients warrant further investigation of [⁶⁸Ga]Ga-HX01 in monitoring antiangiogenic therapy of patients with malignancies.

Clinical trial registration: ClinicalTrials.gov, NCT06416774. Registered 11 May, 2024.