title: Feasibility of islet magnetic resonance imaging using ferumoxytol in intraportal islet transplantation.
abstract: There is a clinical need for an alternative labeling agent for magnetic resonance imaging (MRI) in islet transplantation. We aimed to evaluate the feasibility of islet MRI using ferumoxytol, which is the only clinically-available ultrasmall superparamagnetic iron oxide. We compared islet function and viability of control islets and islets labeled with ferumoxytol and/or a heparin-protamine complex (HPF). Efficacy of ferumoxytol labeling was assessed in both ex vivo and in vivo models. Labeling for 48 h with HPF, but not up to 800 μg/mL ferumoxytol, deranged ex vivo islet viability and function. The T2∗ relaxation time was optimal when islets were labeled with 800 μg/mL of ferumoxytol for 48 h. Prussian blue stain, iron content assay, transmission electron microscopy (TEM) supported internalization of ferumoxytol particles. However, the labeling intensity in the ex vivo MRI of islets labeled with ferumoxytol was much weaker than that of islets labeled with ferucarbotran. In syngeneic intraportal islet transplantation, there was a correlation between the total area of visualized islets and the transplanted islet mass. In conclusion, islet MRI using ferumoxytol was feasible in terms of in vitro and in vivo efficacy and safety. However, the weak labeling efficacy is still a hurdle for the clinical application.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Sang-Man
authors.initials: SM
authors.lastname: Jin
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, Republic of Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, Republic of Korea.
authors.forename: Bae Jun
authors.initials: BJ
authors.lastname: Oh
authors.affiliation: Medical Research Institute, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Shim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, Republic of Korea.
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Dongkyeom
authors.initials: D
authors.lastname: Yoo
authors.affiliation: BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Institute for Bioengineering and Biopharmaceutical Research, Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Yong Hwa
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Institute for Bioengineering and Biopharmaceutical Research, Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: DongYunLee@Hanyang.ac.kr.
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea. Electronic address: jaehyeon@skku.edu.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival; D003287:Contrast Media / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D005295:Ferrocyanides / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D007515:Islets of Langerhans / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D011479:Protamines / Q000737:chemistry; D014185:Transplantation, Isogeneic
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D005295:Ferrocyanides; D011479:Protamines; C000499:ferric oxide; D006493:Heparin; D007501:Iron; C000170:ferric ferrocyanide; D052203:Ferrosoferric Oxide
keywords: Islet; Magnetic resonance imaging; Nanoparticle; Transplantation