A Hyperpolarized Xenon Based Contrast Agent Using a Modified M13 Bacteriophage Scaffold

Todd K. Stevens¹, Krishnan K. Palaniappan¹, Zachary M. Carrico¹, Richard M. Ramirez¹, Matthew B. Francis¹, David E. Wemmer¹, Alexander Pines¹

Molecular imaging aims to detect the presence and spatial distribution of specific biomarkers in tissue. However, for many diseases the detection of these biomarkers must be done at very low concentrations to maximize diagnostic and prognostic value. Due to lack of sensitivity in conventional MRI techniques, exogenous contrast agents (e.g. SPIO, PARACEST) are being widely studied to lower concentration detection thresholds. Recently, targeted hyperpolarized xenon-based biosensors that exploit the exchange of solvated 129Xe between bulk solution (XeW) and cryptophane-A (CryA) molecular cages (XeC) have demonstrated high sensitivity (1). To build upon this work, a filamentous bacteriophage M13 was chosen as a scaffold upon which a large number of CryA copies could be assembled. M13 bacteriophage are routinely employed in phage display techniques used in panning for targeting moieties such as single chain fragment antibodies (scFv) (2), and thus can be straightforwardly targeted to biomarkers allowing for drastically increased CryA payloads per bound target. The purpose of this study was to investigate the feasibility of using an M13 bacteriophage modified with cryptophane-A molecular cages as a sensitive xenon-based MR contrast agent and to determine the detection thresholds of CryA-modified phage.