A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [ 177 Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer.

Autor: Zang J; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China., Wang G; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China.; 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., Zhao T; Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore.; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore.; Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore., Liu H; Department of Nuclear Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China.; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Sichuan Province, Luzhou, 646000, China.; Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan Province, China.; Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, Sichuan Province, China., Lin X; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China., Yang Y; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China., Shao Z; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China., Wang C; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China., Chen H; Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China., Chen Y; Department of Nuclear Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China.; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Sichuan Province, Luzhou, 646000, China.; Institute of Nuclear Medicine, Southwest Medical University, Luzhou, 646000, Sichuan Province, China.; Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, Sichuan Province, China., Zhu Z; 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. 13611093752@163.com., Miao W; Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China. miaoweibing@126.com.; Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China. miaoweibing@126.com.; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China. miaoweibing@126.com., Chen X; Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore. chen.shawn@nus.edu.sg.; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore. chen.shawn@nus.edu.sg.; Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. chen.shawn@nus.edu.sg.; Departments of Surgery, Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117597, Singapore. chen.shawn@nus.edu.sg.; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117597, Singapore. chen.shawn@nus.edu.sg.; Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, 138673, Singapore, Singapore. chen.shawn@nus.edu.sg., Zhang J; Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore. j.zhang@nus.edu.sg.; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore. j.zhang@nus.edu.sg.; Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. j.zhang@nus.edu.sg.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Feb; Vol. 51 (3), pp. 871-882. Date of Electronic Publication: 2023 Oct 21.
DOI: 10.1007/s00259-023-06470-3
Abstrakt: Purpose: This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177 Lu-PSMA-EB-01 (denoted as [ 177 Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods: A total of 13 patients with mCRPC were recruited in this study. A standard 3 + 3 dose escalation protocol was performed. The following dose levels were ultimately evaluated: 1.11, 1.85, and 2.59 GBq/cycle. Patients received [ 177 Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval.
Results: Patients received fractionated doses of [ 177 Lu]Lu-LNC1003 ranging from 1.11 to 2.59 GBq per cycle. Myelosuppression was dose-limiting at 2.59 GBq, and 1.85 GBq was determined to be the MTD. The total-body effective dose for 177 Lu-LNC1003 was 0.35 ± 0.05 mSv/MBq. The salivary glands were found to receive the highest estimated radiation dose, which was calculated to be 3.61 ± 2.83 mSv/MBq. The effective doses of kidneys and red bone marrow were 1.88 ± 0.35 and 0.22 ± 0.04 mSv/MBq, respectively. The tumor mean absorbed doses for bone and lymph node metastases were 8.52 and 9.51 mSv/MBq. Following the first treatment cycle, PSA decline was observed in 1 (33.3%), 4 (66.7%), and 2 (50.0%) patients at dose levels 1 (1.11 GBq), 2 (1.85 GBq), and 3 (2.59 GBq), respectively. Compared with the baseline serum PSA value, 1 (33.3%) at dose level 1 and 4 (66.6%) patients at dose level 2, presented a PSA decline after the second treatment cycle.
Conclusion: This phase 1 trial revealed that the MTD of [ 177 Lu]Lu-LNC1003 is 1.85 GBq. The treatment with multiple cycles at the dose of 1.11 GBq /cycle and 1.85 GBq /cycle was well tolerated. [ 177 Lu]Lu-LNC1003 has higher tumor effective doses in bone and lymph nodes metastases while the absorbed dose in the red bone marrow should be closely monitored in future treatment studies with higher doses and multiple cycles. The frequency of administration also needs to be further explored to assess the efficacy and side effects of [ 177 Lu]Lu-LNC1003 treatment.
Trial Registration: 177 Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic.
Clinicaltrials: gov/ct2/show/NCT05613738.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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