Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE
Abstract Purpose Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmati...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-03-01
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| Series: | EJNMMI Physics |
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| Online Access: | https://doi.org/10.1186/s40658-022-00436-4 |
| _version_ | 1811280197347966976 |
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| author | Javian C. Malcolm Nadia Falzone Jennifer E. Gains Matthew D. Aldridge David Mirando Boon Q. Lee Mark N. Gaze Katherine A. Vallis |
| author_facet | Javian C. Malcolm Nadia Falzone Jennifer E. Gains Matthew D. Aldridge David Mirando Boon Q. Lee Mark N. Gaze Katherine A. Vallis |
| author_sort | Javian C. Malcolm |
| collection | DOAJ |
| description | Abstract Purpose Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [177Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [177Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL). We investigated whether predictions based on an assumption of unchanging AD per unit AA (Gy/GBq) prove robust to cyclical changes in biokinetics. Methods A simulation study, based on dosimetry data from six children with NBL who received four-cycles of [177Lu]Lu-DOTATATE in the LuDO trial (ISRCTN98918118), was performed to explore the effect of variable biokinetics on AD. In the LuDO trial, AA was adapted to the patient’s weight and SPECT/CT-based dosimetry was performed for the kidneys and tumour after each cycle. The largest tumour mass was selected for dosimetric analysis in each case. Results The median tumour AD per cycle was found to decrease from 15.6 Gy (range 8.12–26.4) in cycle 1 to 11.4 Gy (range 9.67–28.8), 11.3 Gy (range 2.73–32.9) and 4.3 Gy (range 0.72–20.1) in cycles 2, 3 and 4, respectively. By the fourth cycle, the median of the ratios of the delivered AD (ADD) and the predicted (or “expected”) AD (ADE) (which was based on an assumption of stable biokinetics from the first cycle onwards) were 0.16 (range 0.02–0.92, p = 0.013) for the tumour and 1.08 (range 0.84–1.76, p > 0.05) for kidney. None of the patients had an objective response at 1 month follow up. Conclusion This study demonstrates variability in Gy/GBq and tumour AD per cycle in children receiving four administrations of [177Lu]Lu-DOTATATE treatment for NBL. NBL is deemed a radiation sensitive tumour; therefore, dose-adaptive treatment planning schemes may be appropriate for some patients to compensate for decreasing tumour uptake as treatment progresses. Trial registration ISRCTN ISRCTN98918118. Registered 20 December 2013 (retrospectively registered). |
| first_indexed | 2024-04-13T01:09:09Z |
| format | Article |
| id | doaj.art-a7f8eaf089e44f72a76a7b42c9598055 |
| institution | Directory Open Access Journal |
| issn | 2197-7364 |
| language | English |
| last_indexed | 2024-04-13T01:09:09Z |
| publishDate | 2022-03-01 |
| publisher | SpringerOpen |
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| series | EJNMMI Physics |
| spelling | doaj.art-a7f8eaf089e44f72a76a7b42c95980552022-12-22T03:09:13ZengSpringerOpenEJNMMI Physics2197-73642022-03-019111410.1186/s40658-022-00436-4Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATEJavian C. Malcolm0Nadia Falzone1Jennifer E. Gains2Matthew D. Aldridge3David Mirando4Boon Q. Lee5Mark N. Gaze6Katherine A. Vallis7Oxford Institute for Radiation Oncology, University of OxfordOxford Institute for Radiation Oncology, University of OxfordDepartment of Oncology, University College London Hospitals NHS Foundation TrustInstitute of Nuclear Medicine, University College London Hospitals NHS Foundation TrustMIM SoftwareOxford Institute for Radiation Oncology, University of OxfordDepartment of Oncology, University College London Hospitals NHS Foundation TrustOxford Institute for Radiation Oncology, University of OxfordAbstract Purpose Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [177Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [177Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL). We investigated whether predictions based on an assumption of unchanging AD per unit AA (Gy/GBq) prove robust to cyclical changes in biokinetics. Methods A simulation study, based on dosimetry data from six children with NBL who received four-cycles of [177Lu]Lu-DOTATATE in the LuDO trial (ISRCTN98918118), was performed to explore the effect of variable biokinetics on AD. In the LuDO trial, AA was adapted to the patient’s weight and SPECT/CT-based dosimetry was performed for the kidneys and tumour after each cycle. The largest tumour mass was selected for dosimetric analysis in each case. Results The median tumour AD per cycle was found to decrease from 15.6 Gy (range 8.12–26.4) in cycle 1 to 11.4 Gy (range 9.67–28.8), 11.3 Gy (range 2.73–32.9) and 4.3 Gy (range 0.72–20.1) in cycles 2, 3 and 4, respectively. By the fourth cycle, the median of the ratios of the delivered AD (ADD) and the predicted (or “expected”) AD (ADE) (which was based on an assumption of stable biokinetics from the first cycle onwards) were 0.16 (range 0.02–0.92, p = 0.013) for the tumour and 1.08 (range 0.84–1.76, p > 0.05) for kidney. None of the patients had an objective response at 1 month follow up. Conclusion This study demonstrates variability in Gy/GBq and tumour AD per cycle in children receiving four administrations of [177Lu]Lu-DOTATATE treatment for NBL. NBL is deemed a radiation sensitive tumour; therefore, dose-adaptive treatment planning schemes may be appropriate for some patients to compensate for decreasing tumour uptake as treatment progresses. Trial registration ISRCTN ISRCTN98918118. Registered 20 December 2013 (retrospectively registered).https://doi.org/10.1186/s40658-022-00436-4[177Lu]Lu-DOTATATEDosimetryInter-cyclic changesPharmacokineticsPeptide receptor radionuclide therapyNeuroblastoma |
| spellingShingle | Javian C. Malcolm Nadia Falzone Jennifer E. Gains Matthew D. Aldridge David Mirando Boon Q. Lee Mark N. Gaze Katherine A. Vallis Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE EJNMMI Physics [177Lu]Lu-DOTATATE Dosimetry Inter-cyclic changes Pharmacokinetics Peptide receptor radionuclide therapy Neuroblastoma |
| title | Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE |
| title_full | Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE |
| title_fullStr | Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE |
| title_full_unstemmed | Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE |
| title_short | Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE |
| title_sort | impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving 177lu lu dotatate |
| topic | [177Lu]Lu-DOTATATE Dosimetry Inter-cyclic changes Pharmacokinetics Peptide receptor radionuclide therapy Neuroblastoma |
| url | https://doi.org/10.1186/s40658-022-00436-4 |
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