MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r 1 and r 2. The r 1 and r 2 values of the uniformly distributed modified ferritin were significantly higher (r 1 = 1,290 mM−1 s−1 and r 2 = 5,740 mM−1 s−1) than values observed for wild-type ferritin (e.g., horse spleen, r 1 = 0.674 mM−1 s−1, r 2 = 95.54 mM−1 s−1). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T2 contrast with negligible T1 effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.