First-in-human study of dosimetry, safety and efficacy for [ 177 Lu]Lu-P15-073: a novel bisphosphonate-based radioligand therapy (RLT) agent for bone metastases.

Autor: Zhao R; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China., Lv J; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China., Li M; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510230, China., Xu S; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China., Liang W; Department of Thoracic Oncology and Surgery, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China., Lin X; State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China., Gu D; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510230, China., Zeng G; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510230, China., Jin W; College of Chemistry, Beijing Normal University, Beijing, 100875, China., Yan Q; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China., Zhong H; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China., Alexoff D; Five Eleven Pharma Inc, 3700 Market St., Philadelphia, PA, 19104, USA., Ploessl K; Five Eleven Pharma Inc, 3700 Market St., Philadelphia, PA, 19104, USA., Zhu L; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China. zhulin@bnu.edu.cn.; College of Chemistry, Beijing Normal University, Beijing, 100875, China. zhulin@bnu.edu.cn., Kung HF; Five Eleven Pharma Inc, 3700 Market St., Philadelphia, PA, 19104, USA. kunghf@gmail.com.; Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA. kunghf@gmail.com., Wang X; Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China. 71lu@163.com.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Oct 18. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1007/s00259-024-06942-0
Abstrakt: Purpose: Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [ 177 Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases.
Methods: Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [ 177 Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [ 99m Tc]Tc-MDP bone scans. Serial planar whole-body scans monitored biodistribution over a 14-day period. Dosimetry was assessed for major organs and tumor lesions, while safety was evaluated through blood biomarkers and pain scores.
Results: Serial planar whole-body scans demonstrated rapid and substantial accumulation of [ 177 Lu]Lu-P15-073 in bone metastases, with minimal uptake in blood and other organs. The absorbed dose in the critical organ, red marrow, was measured at (0.034 ± 0.010 mSv/MBq), with a notably low normalized effective dose (0.013 ± 0.005 mSv/MBq) compared to other 177 Lu-labeled bisphosphonates. Persistent high uptake in bone metastases was observed, resulting in elevated tumor doses (median 3.12 Gy/GBq). Patients exhibited favorable tolerance to [ 177 Lu]Lu-P15-073 therapy, with no new instances of side effects. Additionally, 87.5% (7/8) of patients experienced a significant reduction in pain scale (numerical rating scale, NRS, from 5.1 ± 2.3 to 3.0 ± 1.8). The tumor-background ratio (TBRmean) of [ 99m Tc]Tc-MDP correlated significantly with [ 177 Lu]Lu-P15-073 uptake (P < 0.01), indicating its potential for prediction of absorbed dose.
Conclusions: This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [ 177 Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [ 177 Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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