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

• Published in: Scientific reports 2024-05, Vol.14 (1), p.11959-11, Article 11959
• Main Authors: Bennett, Stephanie, Verry, Camille, Kaza, Evangelia, Miao, Xin, Dufort, Sandrine, Boux, Fabien, Crémillieux, Yannick, de Beaumont, Olivier, Le Duc, Géraldine, Berbeco, Ross, Sudhyadhom, Atchar
• Format: Article
• Language: English
• Subjects: 631/67/1059/485; 639/925/350/354; Adult; Aged; Bioaccumulation; Brain cancer; Brain mapping; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - secondary; Clinical trials; Contrast Media - pharmacokinetics; Double-Blind Method; Female; Gadolinium; Gadolinium - administration & dosage; Gadolinium - metabolism; Humanities and Social Sciences; Humans; Life Sciences; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Metastases; Metastasis; Middle Aged; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; NCT; NCT04899908; Neuroimaging; Patients; Phantoms, Imaging; Placebos; Radiation therapy; Science; Science (multidisciplinary); Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62389-1

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 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient 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 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 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.