Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging

Abstract AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom...

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Main Authors: Stephanie Bennett, Camille Verry, Evangelia Kaza, Xin Miao, Sandrine Dufort, Fabien Boux, Yannick Crémillieux, Olivier de Beaumont, Géraldine Le Duc, Ross Berbeco, Atchar Sudhyadhom
Format: Article
Language:English
Published: Nature Portfolio 2024-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-62389-1
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author Stephanie Bennett
Camille Verry
Evangelia Kaza
Xin Miao
Sandrine Dufort
Fabien Boux
Yannick Crémillieux
Olivier de Beaumont
Géraldine Le Duc
Ross Berbeco
Atchar Sudhyadhom
author_facet Stephanie Bennett
Camille Verry
Evangelia Kaza
Xin Miao
Sandrine Dufort
Fabien Boux
Yannick Crémillieux
Olivier de Beaumont
Géraldine Le Duc
Ross Berbeco
Atchar Sudhyadhom
author_sort Stephanie Bennett
collection DOAJ
description Abstract AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( $${T}_{1}$$ T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient $${T}_{1}$$ T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1–5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in $${T}_{1}$$ T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via $${T}_{1}$$ T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy. Clinical Trial Registration Number: NCT04899908. Clinical Trial Registration Date: 25/05/2021.
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spelling doaj-art-293759d42a3e475ba20a25ec8fdc98f82025-08-20T01:57:49ZengNature PortfolioScientific Reports2045-23222024-05-0114111110.1038/s41598-024-62389-1Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imagingStephanie Bennett0Camille Verry1Evangelia Kaza2Xin Miao3Sandrine Dufort4Fabien Boux5Yannick Crémillieux6Olivier de Beaumont7Géraldine Le Duc8Ross Berbeco9Atchar Sudhyadhom10Brigham and Women’s Hospital|Dana-Farber Cancer Institute|Harvard Medical SchoolUniversité Grenoble Alpes, CHU Grenoble Alpes, Service de Radiothérapie, Inserm UA7Brigham and Women’s Hospital|Dana-Farber Cancer Institute|Harvard Medical SchoolSiemens Medical Solutions USA Inc.NH TherAguix SANH TherAguix SANH TherAguix SANH TherAguix SANH TherAguix SABrigham and Women’s Hospital|Dana-Farber Cancer Institute|Harvard Medical SchoolBrigham and Women’s Hospital|Dana-Farber Cancer Institute|Harvard Medical SchoolAbstract AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( $${T}_{1}$$ T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient $${T}_{1}$$ T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1–5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in $${T}_{1}$$ T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via $${T}_{1}$$ T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy. Clinical Trial Registration Number: NCT04899908. Clinical Trial Registration Date: 25/05/2021.https://doi.org/10.1038/s41598-024-62389-1
spellingShingle Stephanie Bennett
Camille Verry
Evangelia Kaza
Xin Miao
Sandrine Dufort
Fabien Boux
Yannick Crémillieux
Olivier de Beaumont
Géraldine Le Duc
Ross Berbeco
Atchar Sudhyadhom
Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
Scientific Reports
title Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
title_full Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
title_fullStr Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
title_full_unstemmed Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
title_short Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
title_sort quantifying gadolinium based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging
url https://doi.org/10.1038/s41598-024-62389-1
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