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.