“Ferric carboxymaltose has a higher distribution into myocardium than gadobutrol – a quantitative T1 mapping study in healthy volunteers”

Background The dynamic tissue distribution of the clinically available intravenous iron substitution agent ferric carboxymaltose (FCM) is largely unknown. Notably, T1 mapping cardiovascular magnetic resonance (CMR) is highly sensitive for detecting myocardial iron. Purpose To evaluate and quantify the dynamic tissue distribution of FCM using CMR. Materials and methods T1 mapping was prospectively performed to determine T1 and the partition coefficient (lambda) in myocardium, liver, spleen and skeletal muscle up to 60 minutes after onset of a 15-minute-long infusion of 20 ml (50 mg iron/ml) FCM in healthy male volunteers. For comparison, myocardial lambda for gadobutrol (0.2 mmol/kg) was measured in a separate group of age-matched healthy male volunteers. The t-test was used for group comparisons. Results A total of 25 healthy male participants (mean±SD age 27±3 years) were evaluated. Subjects underwent CMR with intravenous FCM (n=8) or gadobutrol (n=17, age matched). T1 values of myocardium, blood, liver, spleen and skeletal muscle were all shortened after intravenous injection of FCM (p<0.001 for all). Lambda for FCM in myocardium and spleen remained constant over time after injection of FCM (mean±SEM 64±8% and 81±20%, respectively, 30 minutes after injection start), while lambda for FCM in liver and skeletal muscle increased over time. Myocardial lambda for FCM was higher than myocardial lambda for gadobutrol (64±8 vs 45±1%, p=0.003). Conclusions T1 mapping can detect and quantify the dynamic tissue distribution of iron from ferric carboxymaltose in the myocardium, liver, spleen and skeletal muscle. Lambda in healthy myocardium for ferric carboxymaltose was markedly higher than lambda for gadobutrol, indicating that ferric carboxymaltose distributes to a greater extent into the myocardium than extracellular contrast agents, most likely due to additional distribution into the intracellular space. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial EudraCT: 2014-002455-26 ### Funding Statement The research was funded in part by the Swedish Research Council, Swedish Heart and Lung Foundation, the Stockholm County Council and Karolinska Institute ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Stockholm Regional Board of Ethics, application number 2014/1140-31/3. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript * BMI : body mass index BSA : body surface area FCM : ferric carboxymaltose LV : left ventricle MOLLI : Modified Look-Locker Inversion-recovery SD : standard deviation SEM : standard error of the mean