Assessment of human islet labeling with clinical grade iron nanoparticles prior to transplantation for graft monitoring by MRI.
Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80-90% purity) were incubated for 24 h with various concentrations of SPIOs (14-280 μg/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 ± 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for >8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.
Ris
Frederic
F
Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, School of Medicine, 4 rue Gabrielle-Perret-Gentil, Geneva 14, Switzerland. frederic.ris@hcuge.ch
Lepetit-Coiffe
Matthieu
M
Meda
Paolo
P
Crowe
Lindsey A
LA
Toso
Christian
C
Armanet
Mathieu
M
Niclauss
Nadja
N
Parnaud
Géraldine
G
Giovannoni
Laurianne
L
Bosco
Domenico
D
Morel
Philippe
P
Vallee
Jean-Paul
JP
Berney
Thierry
T
D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D003287:Contrast Media; D003911:Dextrans; D007328:Insulin; D058185:Magnetite Nanoparticles; D000242:Cyclic AMP; D007501:Iron; C065507:ferumoxides; D005947:Glucose