Real-time detection of bio-event in whole animals provides essential information for understanding biological and therapeutic processes. Magnetic resonance (MR) imaging represents a non-invasive approach to generating three-dimensional anatomic images with high spatial-temporal resolution and unlimited depth penetration. We have developed several self-immolative enzyme-activatable agents that provide excellent in vivo contrast and function as gene expression reporters. Here, we describe a vast improvement in image contrast over our previous generations of these bioresponsive agents based on a new pyridyl-carbamate Gd(III) complex. The pyridyl-carbamate-based agent has a very low MR relaxivity in the “off-state” (r1 = 1.8 mM-1 s-1 at 1.41 T). However, upon enzymatic processing, it generates a significantly higher relaxivity with a Δr1 = 106% versus Δr1 ∼ 20% reported previously. Single X-ray crystal and nuclear magnetic relaxation dispersion analyses offer mechanistic insights regarding MR signal enhancement at the molecular scale. This work demonstrates a pyridyl-carbamate-based self-immolative molecular platform for the construction of enzymatic bio-responsive MR agents, which can be adapted to a wide range of other targets for exploring stimuli-responsive materials and biomedical applications.
ASJC Scopus subject areas
- Colloid and Surface Chemistry
FingerprintDive into the research topics of 'Molecular Engineering of Self-Immolative Bioresponsive MR Probes'. Together they form a unique fingerprint.
Tang, J. (Contributor), Li, H. (Contributor), Yuan, C. (Contributor), Parigi, G. (Contributor), Luchinat, C. (Contributor) & Meade, T. J. (Contributor), Cambridge Crystallographic Data Centre, 2023