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

OBJECTIVES: The 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). METHODS: Sixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one...

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Autores principales: Bussi, Simona, Coppo, Alessandra, Celeste, Roberto, Fanizzi, Antonello, Fringuello Mingo, Alberto, Ferraris, Andrea, Botteron, Catherine, Kirchin, Miles A., Tedoldi, Fabio, Maisano, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000570/
https://www.ncbi.nlm.nih.gov/pubmed/32020385
http://dx.doi.org/10.1186/s13244-019-0824-5
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author Bussi, Simona
Coppo, Alessandra
Celeste, Roberto
Fanizzi, Antonello
Fringuello Mingo, Alberto
Ferraris, Andrea
Botteron, Catherine
Kirchin, Miles A.
Tedoldi, Fabio
Maisano, Federico
author_facet Bussi, Simona
Coppo, Alessandra
Celeste, Roberto
Fanizzi, Antonello
Fringuello Mingo, Alberto
Ferraris, Andrea
Botteron, Catherine
Kirchin, Miles A.
Tedoldi, Fabio
Maisano, Federico
author_sort Bussi, Simona
collection PubMed
description OBJECTIVES: The 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). METHODS: Sixty-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. RESULTS: Significantly (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. CONCLUSIONS: Less 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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spelling pubmed-70005702020-02-21 Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats Bussi, Simona Coppo, Alessandra Celeste, Roberto Fanizzi, Antonello Fringuello Mingo, Alberto Ferraris, Andrea Botteron, Catherine Kirchin, Miles A. Tedoldi, Fabio Maisano, Federico Insights Imaging Original Article OBJECTIVES: The 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). METHODS: Sixty-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. RESULTS: Significantly (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. CONCLUSIONS: Less 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. Springer Berlin Heidelberg 2020-02-04 /pmc/articles/PMC7000570/ /pubmed/32020385 http://dx.doi.org/10.1186/s13244-019-0824-5 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Bussi, Simona
Coppo, Alessandra
Celeste, Roberto
Fanizzi, Antonello
Fringuello Mingo, Alberto
Ferraris, Andrea
Botteron, Catherine
Kirchin, Miles A.
Tedoldi, Fabio
Maisano, Federico
Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title_full Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title_fullStr Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title_full_unstemmed Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title_short Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
title_sort macrocyclic mr contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000570/
https://www.ncbi.nlm.nih.gov/pubmed/32020385
http://dx.doi.org/10.1186/s13244-019-0824-5
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