gms | German Medical Science

Objective: The application of superparamagnetic iron oxide nanoparticles (SPION) for diagnostic procedures has gained wide acceptance. Different utilization of SPIONs is based on two major advantages of iron oxides: their low toxicity to human beings and their high magnetization potential. If exposed to an alternating magnetic field, the harmless iron oxide particles become powerful heat sources by transforming the electromagnetic energy into thermal energy. This heat transmission can be used for the development of minimally invasive sutureless surgery. For these purposes we analyzed the pathway of SPIONs in an in-vivo rat model using MRI, histology and EM over a period of 6 months.

Methods: Different concentrations of SPION were quantitatively analyzed in a 3T MR for their signal alteration (T2 relaxometry a multi-contrast spin echo (SE ) sequence and R2*). A SPION-albumin complex, developed for tissue soldering, was implanted subcutaneously into the rat (n=25 in three groups and followed up 6 months using MR-Tracking and histological analysis of local implant site, brain and liver. Further EM analysis of the Kupffer cells of the liver and of the macrophages locally at the site of implantation was performed. Electromagnetically heated and non heated SPION-albumin complexes were studied separately.

Results: MR-Tracking was useful for quantification and for spotting the local subcutaneous implantation. Tracking of SPIONs in the rest of the rat body provided, no signal alterations and therefore showed that if particles were degraded, then below the very low and sensitive threshold of the MR apparatus. In addition no pathological response was observed for all the investigated organs such as brain, liver or spleen. Liver changes in the number of Kupffer cells were found but completely identical in the SPION treated and sham-operated animals and most likely due to the trauma from surgery. Long-term results showed good fibroblastic in-growth of the implant and no foreign body reaction. The SPION-albumin complex is slowly reabsorbed over the observation period. All the rats were completely unaffected in their normal behavior and food intake.

Conclusions: SPIONs used for tissue soldering have no effect on the normal behavior of rats. SPION-albumin complex is likely to be absorbed very slowly over time by the macrophage system and has no toxic effects on the brain, liver and spleen over a period of 6 month post implantation. Whole body MR Tracking of the SPION is below the sensitivity level and therefore unsuitable.