We propose to perform MRI and SQUID imaging using targeted magnetic nanoparticle contrast agents. The contrast enhancement for the imaging will be provided by superparamagnetic nanoparticles approximately 6 nm in diameter. Cellular targeting of the contrast agent is accomplished by conjugating the nanoparticles to folate molecules on a dendrimer scaffold. Internalization of the contrast agent is through the high-affinity folate receptor, which is overexpressed in a variety of epithelial cancers. Due to recycling of the folate receptor, the cells can internalize high numbers of nanoparticles. In vitro and in vivo cellular uptake levels of the nanoparticles will be determined by magnetic measurements. For in vivo imaging, immune compromised mouse will be injected with human KB squameous carcinoma cells as a disease model. After introduction of the contrast agent, MR imaging will be performed. Similarly, detection of the superparamagnetic particles both in vitro and in vivo will be performed to determine the ultimate limits of the SQUID imaging technique. Estimates place the limit at approximately 1000 cells for a tumor 5 cm from the SQUID detector. This approach allows the imagining of pre-clinical lesions, and paves the way for intracellular delivery of functional imaging agents.
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