Ruiyue Zhao, Jie Lv, Mingzhao Li, Siran Xu, Wenhua Liang, Xinqing Lin, Di Gu, Guohua Zeng, Wenbin Jin, Qingsong Yan, Huizhen Zhong, David Alexoff, Karl Ploessl, Lin Zhu, Hank F. Kung, Xinlu Wang
{"title":"对[177Lu]Lu-P15-073（一种基于双膦酸盐的新型放射性配体疗法（RLT）药物）的剂量测定、安全性和疗效进行首次人体研究","authors":"Ruiyue Zhao, Jie Lv, Mingzhao Li, Siran Xu, Wenhua Liang, Xinqing Lin, Di Gu, Guohua Zeng, Wenbin Jin, Qingsong Yan, Huizhen Zhong, David Alexoff, Karl Ploessl, Lin Zhu, Hank F. Kung, Xinlu Wang","doi":"10.1007/s00259-024-06942-0","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [<sup>177</sup>Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [<sup>177</sup>Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [<sup>99m</sup>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.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Serial planar whole-body scans demonstrated rapid and substantial accumulation of [<sup>177</sup>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 <sup>177</sup>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 [<sup>177</sup>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 [<sup>99m</sup>Tc]Tc-MDP correlated significantly with [<sup>177</sup>Lu]Lu-P15-073 uptake (<i>P</i> < 0.01), indicating its potential for prediction of absorbed dose.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [<sup>177</sup>Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [<sup>177</sup>Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"First-in-human study of dosimetry, safety and efficacy for [177Lu]Lu-P15-073: a novel bisphosphonate-based radioligand therapy (RLT) agent for bone metastases\",\"authors\":\"Ruiyue Zhao, Jie Lv, Mingzhao Li, Siran Xu, Wenhua Liang, Xinqing Lin, Di Gu, Guohua Zeng, Wenbin Jin, Qingsong Yan, Huizhen Zhong, David Alexoff, Karl Ploessl, Lin Zhu, Hank F. Kung, Xinlu Wang\",\"doi\":\"10.1007/s00259-024-06942-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [<sup>177</sup>Lu]Lu-P15-073, a novel bisphosphonate, for radioligand therapy (RLT) in bone metastases.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>Ten patients (age 35 to 75) with confirmed bone metastases underwent therapy with a single dose of [<sup>177</sup>Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [<sup>99m</sup>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Serial planar whole-body scans demonstrated rapid and substantial accumulation of [<sup>177</sup>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 <sup>177</sup>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 [<sup>177</sup>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 [<sup>99m</sup>Tc]Tc-MDP correlated significantly with [<sup>177</sup>Lu]Lu-P15-073 uptake (<i>P</i> < 0.01), indicating its potential for prediction of absorbed dose.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>This study demonstrates the safety, dosimetry, and efficacy of a single therapeutic dose of [<sup>177</sup>Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [<sup>177</sup>Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.</p>\",\"PeriodicalId\":11909,\"journal\":{\"name\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2024-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Nuclear Medicine and Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00259-024-06942-0\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-024-06942-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
First-in-human study of dosimetry, safety and efficacy for [177Lu]Lu-P15-073: a novel bisphosphonate-based radioligand therapy (RLT) agent for bone metastases
Purpose
Bisphosphonates are pivotal in managing bone tumors by inhibiting bone resorption. This study investigates the therapeutic potential of [177Lu]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 [177Lu]Lu-P15-073 (1,225 ± 84 MBq, or 33 ± 2 mCi). Prior to treatment, bone metastases were verified via [99mTc]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 [177Lu]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 177Lu-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 [177Lu]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 [99mTc]Tc-MDP correlated significantly with [177Lu]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 [177Lu]Lu-P15-073 in bone metastases. The treatment was well-tolerated with no severe adverse events. These findings suggest that [177Lu]Lu-P15-073 holds promise as a novel RLT agent for bone metastases.
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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