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

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.

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.

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.

[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.

ClinicalTrials.gov, NCT06416774. Registered 11 May, 2024.