In vivo visualization of single native pancreatic islets in the mouse

Abstract

The purpose of this study was to investigate the potential of a novel targeted contrast agent (CA) for the in vivo visualization of single native pancreatic islets, the sites of insulin production, in the pancreas of mice using magnetic resonance imaging (MRI). The CA for intravenous administration was composed of the β-cell-specific single-chain antibody fragment, SCA B1, and ferromagnetic carbon-coated cobalt nanoparticles. MRI experiments were performed at 7, 9.4 and 16.4 T in excised organs (pancreas, liver, kidney, spleen), at 7 T in mice fixed in formalin and at 9.4 and 16.4 T in living mice. Image contrast in untreated control animals was compared with images from mice treated with unspecific and specific CA. For the validation of MRI results, selected pancreases were subjected to immunohistochemical staining and numerical contrast simulations were performed. Ex vivo results and the outcome of immunohistochemistry suggest that islets are marked only by the CA containing SCA B1. Strong accumulation of particles was found also in other investigated organs owing to the uptake by the reticuloendothelial system, but the contrast in the MR images is clearly distinguishable from the islet specific contrast in pancreases and numerical predictions. In vivo experiments based on averaged dynamic sampling with 66 × 66 × 100 µm³ and triggered acquisition with 90 × 90 × 200 µm³ nominal resolution resulted in similar particle contrast to in in vitro measurements. The newly developed CA and MRI strategies have the potential to be used for studying mouse diabetes models by visualizing single native pancreatic islets.

Targeting GLP-1 receptors for repeated magnetic resonance imaging differentiates graded losses of pancreatic beta cells in mice

“…The data provide a significant step towards the validation of a probe monitoring the effect of candidate treatments in a pre-clinical setting, assuming that the expression of GLP-1rs is not altered under different glycaemic conditions [ 43 ]. Such pre-clinical studies should further benefit from the exquisite resolution achieved with high magnetic field MRI, which now allows for the visualisation of individual islets within an intact pancreas [ 21 , 23 ].…”

“…In the search for alternatives, several studies have investigated MRI [ 20 – 22 ], a method that does not involve ionising radiation. The modality provides for an unsurpassed anatomical visualisation of soft tissues, including individual islets in experimental models when high magnetic fields are used [ 21 , 23 ]. Still, MRI has a significantly lower sensitivity than either PET or SPECT, and hardly allows for an absolute quantitative evaluation of the signal [ 2 , 3 ].…”

3-Dimensional histological reconstruction and imaging of the murine pancreas

“…We have demonstrated that, using the methods presented in this report, this size and spatial variation is readily captured. Further, the murine pancreas is a complex structure and differs significantly from that of other mammals, including man (Islam 2010; Balla et al 2013). The mouse pancreas is sparse and extends along the big curvature of the stomach, contacting its thick tail (left lobe) with the spleen, whereas while the human pancreas topography is similar, it is a more compact gland and its tail is the thinner part of the organ.…”

Pancreatic β‐cell imaging in humans: fiction or option?

“…IC2, a rat monoclonal IgM Ab, which targets sphingomyelin on the β‐cell surface . Single‐chain antibodies (SCA), such as SCA‐B1 . The target of SCA‐B1 is not known but was shown specific for β cells and suitable for MRI, after coupling it with highly magnetic cobalt nanoparticles . Less specifically, hydroxy‐tryptophan targets the serotonergic innervation, which is present in all the endocrine cells of the pancreas ; however, in spite of their wide expression, this probe appeared to show a correlation between β‐cell mass and pancreatic signal in STZ‐treated rats and have been able to differentiate people with T1DM from healthy people Somatostatin receptors were also proposed as a target for imaging probes to monitor β‐cell mass. Thus, Sako et al.…”

“…• Single-chain antibodies (SCA), such as SCA-B1 [107]. The target of SCA-B1 is not known but was shown specific for cells and suitable for MRI, after coupling it with highly magnetic cobalt nanoparticles [34].…”