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Objective: Superparamagnetic iron oxide (SPIO) nanoparticles have been used to label cells for in vivo monitoring by magnetic resonance imaging (MRI). The purpose of the is study was to determine tumor cell viability and toxicity after iron incorporation in vitro, and to evaluate the in vivo growth, imaging, and histopathology of magnetically labeled LX-1 human small cell lung carcinoma (SCLC) cells in a rat brain tumor model. Methods: LX-1 SCLC cells were labeled with ferumoxides (Feridex IV, 10-100 μg/ml) with or without protamine sulfate (10 μg/ml). Iron histochemistry was evaluated on fixed cells and whole cell lysates were assessed for apoptosis by Western blot analysis. Iron-labeled LX-1 SCLC cells were implanted into the right cerebral hemisphere of nude rats. Serial MRI (T1, T2, GRET2*, FLAIR) scans were obtained 6, 8-9, and 13 days after implantation. Neuropathological analysis and DAB-enhanced Perl’s stain for iron were performed after the final MRI. Results: The combination of protamine sulfate and ferumoxides gave enhanced iron staining that was detectable for 3 weeks without significant apoptotic effect as indicated by PARP cleavage. SPIO labeled LX-1 SCLC intracerebral tumors were identified at 6 days after implantation, and both the intensity and the volume of distribution of iron signal were dose dependent. Iron MR signal progressively faded by 13 days after implantation. Histochemistry localized much of the iron to the inoculation needle track and to necrotic areas within the tumor, while tumor cells showed progressively less iron labeling to the periphery of the tumor. Conclusions: Polycationic transfection agent (protamine sulfate) facilitates cellular iron loading without causing significant toxicity in vitro. This ferumoxides:protamine complex labeling technique may provide a useful tool for tracking transplanted tumor cells, particularly micrometastases that are difficult to image with conventional MRI.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]