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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 52; no. 4; pp. 1293 - 1304
• Main Authors: Zhang, Xiao, Fang, Hanyi, Yang, Biao, Qin, Chunxia, Hu, Fan, Ruan, Weiwei, Chen, Jing, Zeng, Dexing, Gai, Yongkang, Lan, Xiaoli
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2025; Springer Nature B.V
• Subjects: Adult; Aged; Angiogenesis; Blood; Cardiology; CD13 antigen; Computed tomography; Dosimetry; Evaluation; Female; Gallium Radioisotopes; Half-life; Healthy Volunteers; Humans; Imaging; Integrin alphaVbeta3 - metabolism; Lesions; Male; Malignancy; Medicine; Medicine & Public Health; Metastases; Middle Aged; Neoplasms - diagnostic imaging; Neoplasms - metabolism; Nuclear Medicine; Oncology; Original Article; Orthopedics; Pharmaceuticals; Pharmacokinetics; Positron emission; Positron Emission Tomography Computed Tomography; Radiochemical analysis; Radioisotopes; Radiology; Renal function; Tissue Distribution; Tumors; Urine; Vascularization; Dual-targeting; Malignancy; [; Safety; PET; Ga]Ga-HX01; [68Ga]Ga-HX01
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-07002-3

Purpose Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]Ga-HX01 were assessed. Results In phase Ia study, [ 68 Ga]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, [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]Ga-HX01 in monitoring antiangiogenic therapy of patients with malignancies. Clinical trial registration ClinicalTrials.gov, NCT06416774. Registered 11 May, 2024.