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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. Newly developed intelligent magnetic nanoparticles (Therma-Max®) are coated with thermo-responsive polymers and show a reversible transition between dispersion and flocculation as a function of temperature. Our hypothesis is that the thermo-responsive magnetic nanoparticles are small enough to enter the lymphatic vessels, flocculate due to body temperature, and become large enough to be specifically retained in the SLNs. In this study, we investigated the capability of MRI using thermo-responsive magnetic nanoparticles for detection of SLNs.
 Materials and methods
 Three types of magnetic nanoparticles were examined; the thermo-responsive magnetic nanoparticles flocculating at 36 °C, those flocculating at 42 °C, and those flocculating at 55 °C. All these nanoparticles were around 100 nm in diameter. Pre- and postcontrast MRI were obtained following injection into the subserosa of cecum in rats. The injection sites, the SLNs, and the distant lymph nodes were resected and histologically examined at 5 min, 1 h, 4 h, 8 h, 12 h, 24 h, 2 days, 3 days, 5 days, and 7 days after injection.
 Results
 Histological evaluation revealed that the magnetic nanoparticles flocculating at 36 °C were observed only at the injection site, because they flocculated due to body temperature, and did not flow to the SLNs. The magnetic nanoparticles flocculating at 42 °C were found both at the injection site and at the SLNs, but not at the distant lymph nodes. They entered lymphatic vessels, gradually flocculated due to body temperature, and became large enough to be retained in the SLNs. The magnetic nanoparticles flocculating at 55°C were found at all of the injection site, the SLNs, and the distant lymph nodes. They did not flocculate and flew to the distant lymph nodes. Post-contrast MRI showed that the signal-to-noise ratio in SLNs was significantly lower than that found on precontrast images after injection of thermo-responsive magnetic nanoparticles flocculating at 42 °C.
 Conclusion
 The present study showed that thermo-responsive magnetic nanoparticles could target sentinel lymph nodes by adjusting the temperature at which they flocculate. Magnet resonance lymphography with thermo-responsive magnetic nanoparticles enables visualization of SLNs. This method will reduce the labeling of non-SLN which was seen in the previously reported interstitial magnet resonance lymphography.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA