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.

中文翻译：

---

[68Ga]Ga-HX01 靶向整合素 αvβ3 和 CD13 在健康和恶性肿瘤受试者中的 I 期研究

 目的

无创血管生成可视化对于评估肿瘤增殖、进展、侵袭和转移至关重要。本研究旨在将靶向新生血管形成中整合素 αvβ 3 和 CD13 的异二聚体 PET 示踪剂 [⁶⁸Ga]Ga-HX01 转化为 I 期临床研究。

 方法

本研究招募了 12 名健康志愿者 （Ia 期） 和 10 名恶性肿瘤患者 （Ib 期）。将 Ia 期受试者分为低剂量组 （0.05 mCi/kg） 和高剂量组 （0.1 mCi/kg）。对于 Ia 期受试者，收集 PET/CT 图像、血液和尿液样本以分析 [⁶⁸Ga]Ga-HX01 的生物分布、药代动力学、辐射剂量测定和安全性。对于 Ib 期患者，在注射后 30 ± 5 和 60 ± 5 min 进行 PET/MR 扫描。评价 [⁶⁸Ga]Ga-HX01 的安全性和初步诊断价值。

 结果

在 Ia 期研究中，[⁶⁸Ga]Ga-HX01 在两个剂量组中的分布和代谢相似，在肾脏和尿液中积累最高。它具有快速的肾脏排泄和血液清除率，消除半衰期 （T_1/2） 为 28.92 ± 3.97 分钟。总有效剂量为 2.14 × 10^{− 2} mSv/MBq。在 Ib 期研究中，[⁶⁸Ga]Ga-HX01 清楚地检测到每位患者的病灶，共发现 59 个不同摄取水平的病灶。对于安全性评价，检查过程中未观察到严重不良事件。

 结论

[⁶⁸加]Ga-HX01 已被证明是一种转化放射性药物，具有可靠的安全性、良好的药代动力学和可视化肿瘤的能力。恶性肿瘤患者的初步结果值得进一步研究 [⁶⁸Ga]Ga-HX01 在监测恶性肿瘤患者抗血管生成治疗中的应用。

临床试验注册

ClinicalTrials.gov，NCT06416774。注册于 2024 年 5 月 11 日。