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

Abstract

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 r1 and r2. The r1 and r2 values of the uniformly distributed modified ferritin were significantly higher (r1 = 1,290 mM−1 s−1 and r2 = 5,740 mM−1 s−1) than values observed for wild-type ferritin (e.g., horse spleen, r1 = 0.674 mM−1 s−1, r2 = 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.