title: Safety profiles of gadolinium chelates in juvenile rats differ according to the risk of dissociation.
abstract: This study was designed to compare the safety of two gadolinium chelates (GCs), used as contrast agents for magnetic resonance imaging, in juvenile rats. Juvenile rats received five intravenous administrations (between postnatal day [PND] 4 and 18) of gadoteric acid (macrocyclic ionic GC), gadodiamide (linear nonionic GC) or saline, and sacrificed at PND 25. Gadodiamide induced mortality, alopecia and hyperpigmentation of dorsal skin. Two gadodiamide-treated rats presented severe epidermal and dermal lesions. No abnormal signs were detected following administration of gadoteric acid. Higher tissue gadolinium concentrations were found in the gadodiamide group compared to the gadoteric acid group. Dissociation of gadodiamide was observed in skin and liver, with the presence of dissociated and soluble gadolinium. In conclusion, repeated administration of gadoteric acid was well tolerated by juvenile rats. In contrast, gadodiamide induced significant toxicity and more marked tissue gadolinium retention (at least partly in the dissociated and soluble form).
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: nathalie.fretellier@guerbet-group.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fretellier
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: maazouz.meryam@gmail.com.
authors.forename: Meryam
authors.initials: M
authors.lastname: Maazouz
authors.affiliation: Atlantic Bone Screen, 44800 Saint Herblain, France. Electronic address: alexandrine.luseau@atlantic-bone-screen.com.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Luseau
authors.affiliation: Atlantic Bone Screen, 44800 Saint Herblain, France. Electronic address: fannie.baudimont@atlantic-bone-screen.com.
authors.forename: Fannie
authors.initials: F
authors.lastname: Baudimont
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: gaelle.jestin-mayer@guerbet-group.com.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Jestin-Mayer
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: simon.bourgery@guerbet-group.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Bourgery
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: marlene.rasschaert@gmail.com.
authors.forename: Marlène
authors.initials: M
authors.lastname: Rasschaert
authors.affiliation: Department of Pathology, Hôpital Européen Georges Pompidou, 75015 Paris, France; INSERM U970, Department of Pathology, Hôpital Européen Georges Pompidou, 75015 Paris, France. Electronic address: patrick.bruneval@egp.aphp.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: cecile.factor@guerbet-group.com.
authors.forename: Cécile
authors.initials: C
authors.lastname: Factor
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: fatiha.mecieb@gmail.com.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Mecieb
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: jean-marc.idee@guerbet-group.com.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Idée
authors.affiliation: Guerbet, Research & Innovation Division, 93600 Aulnay-sous-Bois, France. Electronic address: claire.corot@guerbet-group.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D019786:Gadolinium DTPA / Q000378:metabolism / Q000633:toxicity*; D006571:Heterocyclic Compounds / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012306:Risk; D012867:Skin / Q000473:pathology
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C064925:gadodiamide; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D019786:Gadolinium DTPA
keywords: Contrast agents; Gadolinium; Gadolinium chelates; Immaturity of renal function.; Juvenile toxicity; Safety