Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study
Integrin αvβ3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin αvβ3-targeting radionuclide drug with...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383524004131 |
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| author | Huimin Sui Feng Guo Hongfei Liu Rongxi Wang Linlin Li Jiarou Wang Chenhao Jia Jialin Xiang Yingkui Liang Xiaohong Chen Zhaohui Zhu Fan Wang |
| author_facet | Huimin Sui Feng Guo Hongfei Liu Rongxi Wang Linlin Li Jiarou Wang Chenhao Jia Jialin Xiang Yingkui Liang Xiaohong Chen Zhaohui Zhu Fan Wang |
| author_sort | Huimin Sui |
| collection | DOAJ |
| description | Integrin αvβ3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin αvβ3-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin αvβ3-avid tumors were recruited to accept 177Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6–8 weeks. No adverse event over grade 3 was observed. 177Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of 177Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin αvβ3-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses. |
| format | Article |
| id | doaj-art-6d105e7845164ce4ae2c44beab87299e |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-6d105e7845164ce4ae2c44beab87299e2025-08-20T02:47:37ZengElsevierActa Pharmaceutica Sinica B2211-38352025-02-0115266968010.1016/j.apsb.2024.10.012Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human studyHuimin Sui0Feng Guo1Hongfei Liu2Rongxi Wang3Linlin Li4Jiarou Wang5Chenhao Jia6Jialin Xiang7Yingkui Liang8Xiaohong Chen9Zhaohui Zhu10Fan Wang11Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China; Corresponding authors.Department of Nuclear Medicine, Sixth Medical Center of PLA General Hospital, Beijing 100048, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, ChinaDepartment of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, ChinaDepartment of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, ChinaDepartment of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, ChinaDepartment of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, ChinaDepartment of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, ChinaDepartment of Nuclear Medicine, Sixth Medical Center of PLA General Hospital, Beijing 100048, China; Corresponding authors.Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Corresponding authors.Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China; Corresponding authors.Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing 100191, China; Corresponding authors.Integrin αvβ3 is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2, a novel integrin αvβ3-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin αvβ3-avid tumors were recruited to accept 177Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6–8 weeks. No adverse event over grade 3 was observed. 177Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of 177Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin αvβ3-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.http://www.sciencedirect.com/science/article/pii/S2211383524004131177Lu-AB-3PRGD2Integrin αvβ3Targeted radionuclide therapyFirst-in-human studyPharmacokineticsDosimetry |
| spellingShingle | Huimin Sui Feng Guo Hongfei Liu Rongxi Wang Linlin Li Jiarou Wang Chenhao Jia Jialin Xiang Yingkui Liang Xiaohong Chen Zhaohui Zhu Fan Wang Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study Acta Pharmaceutica Sinica B 177Lu-AB-3PRGD2 Integrin αvβ3 Targeted radionuclide therapy First-in-human study Pharmacokinetics Dosimetry |
| title | Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study |
| title_full | Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study |
| title_fullStr | Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study |
| title_full_unstemmed | Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study |
| title_short | Safety, pharmacokinetics, and dosimetry of 177Lu-AB-3PRGD2 in patients with advanced integrin αvβ3-positive tumors: A first-in-human study |
| title_sort | safety pharmacokinetics and dosimetry of 177lu ab 3prgd2 in patients with advanced integrin αvβ3 positive tumors a first in human study |
| topic | 177Lu-AB-3PRGD2 Integrin αvβ3 Targeted radionuclide therapy First-in-human study Pharmacokinetics Dosimetry |
| url | http://www.sciencedirect.com/science/article/pii/S2211383524004131 |
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