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

Sci Rep. 2024 May 25;14(1):11959. doi: 10.1038/s41598-024-62389-1.

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 ) 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / secondary
  • Contrast Media / pharmacokinetics
  • Double-Blind Method
  • Female
  • Gadolinium* / administration & dosage
  • Gadolinium* / metabolism
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Nanoparticles / chemistry
  • Phantoms, Imaging

Substances

  • Gadolinium
  • Contrast Media

Associated data

  • ClinicalTrials.gov/NCT04899908