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Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats

Authors
  • Bussi, Simona1
  • Coppo, Alessandra1
  • Celeste, Roberto1
  • Fanizzi, Antonello1
  • Fringuello Mingo, Alberto1
  • Ferraris, Andrea2
  • Botteron, Catherine3
  • Kirchin, Miles A.4
  • Tedoldi, Fabio1
  • Maisano, Federico2
  • 1 Bracco Imaging SpA, Bracco Research Centre, Via Ribes 5, Colleretto Giacosa, TO, 10010, Italy , Colleretto Giacosa (Italy)
  • 2 Bracco SpA, Via Caduti di Marcinelle 13, Milano, 20134, Italy , Milano (Italy)
  • 3 Sirius Pathology, 1705 route du Salève, Cruseilles, 74350, France , Cruseilles (France)
  • 4 Bracco Imaging SpA, Via Caduti di Marcinelle 13, Milano, 20134, Italy , Milano (Italy)
Type
Published Article
Journal
Insights into Imaging
Publisher
Springer-Verlag
Publication Date
Feb 04, 2020
Volume
11
Issue
1
Identifiers
DOI: 10.1186/s13244-019-0824-5
Source
Springer Nature
Keywords
License
Green

Abstract

ObjectivesThe purpose of this study was to compare Gd levels in rat tissues after cumulative exposure to four commercially available macrocyclic gadolinium-based contrast agents (GBCAs).MethodsSixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one control group (n = 5). Animals in each exposure group received 20 GBCA administrations (four per week of ProHance®, Dotarem®, Clariscan™, or Gadovist® for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After 28-days’ recovery, animals were sacrificed and tissues harvested for Gd determination by inductively coupled plasma-mass spectroscopy (ICP-MS). Histologic assessment of the kidney tissue was performed for all animals.ResultsSignificantly (p ≤ 0.005; all evaluations) lower Gd levels were noted with ProHance® than with Dotarem®, Clariscan™, or Gadovist® in all soft tissue organs: 0.144 ± 0.015 nmol/g vs. 0.342 ± 0.045, 0.377 ± 0.042, and 0.292 ± 0.047 nmol/g, respectively, for cerebrum; 0.151 ± 0.039 nmol/g vs. 0.315 ± 0.04, 0.345 ± 0.053, and 0.316 ± 0.040 nmol/g, respectively, for cerebellum; 0.361 ± 0.106 nmol/g vs. 0.685 ± 0.330, 0.823 ± 0.495, and 1.224 ± 0.664 nmol/g, respectively, for liver; 38.6 ± 25.0 nmol/g vs. 172 ± 134, 212 ± 121, and 294 ± 127 nmol/g, respectively, for kidney; and 0.400 ± 0.112 nmol/g vs. 0.660 ± 0.202, 0.688 ± 0.215, and 0.999 ± 0.442 nmol/g, respectively, for skin. No GBCA-induced macroscopic or microscopic findings were noted in the kidneys.ConclusionsLess Gd is retained in the brain and body tissues of rats 28 days after the last exposure to ProHance® compared to other macrocyclic GBCAs, likely due to unique physico-chemical features that facilitate more rapid and efficient clearance.

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