title: Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles.
abstract: This study was undertaken to investigate the in vitro effect of islet labeling with iron oxide nanoparticles for MRI on islet viability, insulin secretion, and gene expression. Isolated rat islets were labeled with Resovist (25-200 microg Fe/mL, a clinically approved MRI contrast agent) in the presence or absence of poly-l-Lysine (PLL, 1.5 microg/mL) for 48 h. The iron content of labeled islets was found to increase in a dose-dependent manner. More than 90% of the islets were labeled with 100 microg Fe/mL. We confirmed the localizations of iron oxide nanoparticles within islet beta-cells by insulin immunostaining. As the concentration of Resovist increased, T(2) values as determined by T(2)-weighted MRI on a 1.5 Tesla MR scanner decreased. Labeling of 100 islets in a medium containing 100 microg Fe/mL of Resovist in the absence of PLL provided sufficient contrast for islet visualization on T(2)-weighted MRI. MTT assays showed that the viability of labeled islets was not different from that of unlabeled islets. No statistical difference was observed between labeled (2.91 +/- 0.36) and unlabeled islets (2.83 +/- 0.61) in terms of the ability to secrete insulin, as determined by the glucose stimulation index. We also evaluated the effect of iron oxide incorporation on the gene expressions in islet cells using RT-PCR (reverse transcriptase PCR). Insulin expression in labeled islets was significantly elevated (1.83 +/- 0.25 fold vs. unlabeled; p = 0.005), but not the expression of somatostatin (1.39 +/- 0.18 fold vs. unlabeled; p = 0.085) or glucagons (1.28 +/- 0.13 fold vs. unlabeled; p = 0.09). Expression of an important transcription factor for insulin gene transcription, BETA2 (beta-cell E-box trans-activator), was increased in labeled islets (1.67 +/- 0.15 fold vs. unlabeled; p = 0.029). The findings of this study indicate that Resovist provides a satisfactory means to image islets and has no deleterious effect on islet function or gene expression.
authors.affiliation: Diagnostic Radiology, Seoul National University Hospital, Institute of Radiation Medicine, Medical Research Center, Seoul National University, 28, Yeongeon-dong, Jongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Hoe Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: YoonSeok
authors.initials: Y
authors.lastname: Choi
authors.forename: In Chan
authors.initials: IC
authors.lastname: Song
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D003911:Dextrans; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling / Q000379:methods
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; C065507:ferumoxides; D052203:Ferrosoferric Oxide