Xiao Zhang, Hanyi Fang, Biao Yang, Chunxia Qin, Fan Hu, Weiwei Ruan, Jing Chen, Dexing Zeng, Yongkang Gai, Xiaoli Lan
{"title":"[68Ga]Ga-HX01在健康和恶性肿瘤患者中靶向整合素αvβ3和CD13的I期研究","authors":"Xiao Zhang, Hanyi Fang, Biao Yang, Chunxia Qin, Fan Hu, Weiwei Ruan, Jing Chen, Dexing Zeng, Yongkang Gai, Xiaoli Lan","doi":"10.1007/s00259-024-07002-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [<sup>68</sup>Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.</p><p><strong>Methods: </strong>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 [<sup>68</sup>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 [<sup>68</sup>Ga]Ga-HX01 were assessed.</p><p><strong>Results: </strong>In phase Ia study, [<sup>68</sup>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<sub>1/2</sub>) of 28.92 ± 3.97 min. The total effective dose was 2.14 × 10<sup>- 2</sup> mSv/MBq. In phase Ib study, [<sup>68</sup>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.</p><p><strong>Conclusion: </strong>[<sup>68</sup>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 [<sup>68</sup>Ga]Ga-HX01 in monitoring antiangiogenic therapy of patients with malignancies.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT06416774. Registered 11 May, 2024.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"1293-1304"},"PeriodicalIF":8.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phase I study of [<sup>68</sup>Ga]Ga-HX01 for targeting integrin αvβ3 and CD13 in healthy and malignancy subjects.\",\"authors\":\"Xiao Zhang, Hanyi Fang, Biao Yang, Chunxia Qin, Fan Hu, Weiwei Ruan, Jing Chen, Dexing Zeng, Yongkang Gai, Xiaoli Lan\",\"doi\":\"10.1007/s00259-024-07002-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [<sup>68</sup>Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.</p><p><strong>Methods: </strong>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 [<sup>68</sup>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 [<sup>68</sup>Ga]Ga-HX01 were assessed.</p><p><strong>Results: </strong>In phase Ia study, [<sup>68</sup>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<sub>1/2</sub>) of 28.92 ± 3.97 min. The total effective dose was 2.14 × 10<sup>- 2</sup> mSv/MBq. In phase Ib study, [<sup>68</sup>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.</p><p><strong>Conclusion: </strong>[<sup>68</sup>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 [<sup>68</sup>Ga]Ga-HX01 in monitoring antiangiogenic therapy of patients with malignancies.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, NCT06416774. 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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 (T1/2) 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.
期刊介绍：
The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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