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Background

Recent studies have shown the potential of magnetic resonance imaging (MRI) with interstitial administration of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO), although SPIO and USPIO were not retained in sentinel lymph nodes (SLNs). The ideal SLN imaging agent needs to be small enough to enter the lymphatic vessels, yet large enough to be retained in the SLNs.

Our hypothesis is that newly developed intelligent thermo-responsive magnetic nanoparticles (Therma-Max®) are small enough to enter the lymphatic vessels, flocculate according to body temperature, and become large enough to be retained in the SLNs. And that they are useful for SLN mapping with MRI. In this study, we investigated the capability of MRI using thermo-responsive magnetic nanoparticles for optimization of SLNs.

Materials and methods

In study 1, three types of magnetic nanoparticles were examined; the thermo-responsive magnetic nanoparticles flocculating at 36 °C, those flocculating at 42 °C, and the magnetic nanoparticles which were not coated with thermo-responsive polymers. All these three nanoparticles were around 100 nm in diameter. The injection sites, the SLNs, and the distant lymph nodes were resected after these nanoparticles were injected into the subserosa of cecum in rats.

In study 2, pre- and postcontrast MRI were obtained following subdermal injection of thermo-responsive magnetic nanoparticles flocculating at 42 °C into the chest wall in rats.

Results

In study 1, histological evaluation revealed that the magnetic nanoparticles flocculating at 36 °C were observed only at the injection site, because they flocculated according to body temperature and did not migrate to SLNs. The magnetic nanopaticles flocculating at 42 °C were found both at the injection site and at the SLNs, but not at the distant lymph nodes. They flocculated and became large enough to be retained in the SLNs. The magnetic nanoparticles which were not coated with thermo-responsive polymers were found at all of the injection site, the SLNs and the distant lymph nodes.

In study 2, MRI showed that the signal-to-noise ratio in axillary SLNs was significantly lower than that found on precontrast images at 20 minutes after injection of thermo-responsive magnetic nanoparticles flocculating at 42 °C (P < 0.05 ).

Conclusion

>The present study showed that thermo-responsive magnetic nanoparticles could target sentinel lymph nodes by adjusting the temperature at which they flocculate. And that they could be used as an contrast agent for SLN mapping with MRI.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA