“…Examples include enzymes or transporters that can act on synthetic contrast agents, [178] proteins that naturally contain paramagnetic metals, including ferritin, [179] MagA, [180] MntR, [181] tyrosinase, [182] and cytochrome P450, [183] and diamagnetic CEST agents such as lysine rich-protein, [184] human protamine sulfate [185] and proteins that alter water diffusivity in tissue. [186] Comparatively fewer contrast agents have been designed for heteronuclear MRI, all of them based on enzymatic or transporter interactions with 19 F compounds, [187] HP 13 C compounds, [187c, 188] or 31 P substrates. [189] A major challenge of all of these agents is their relatively low molecular sensitivity, typically of the micromolar or higher order, which limits their range of in vivo applications.…”