A Fibrosis-Targeting T₁ MRI Contrast Agent Synthesized via Photooxidative Self-Desulfurization of Porphyrin Thiourea

Fibrosis is a silent disease that becomes untreatable and incurable in late stages, ultimately leading to organ failure. Early intervention can slow or even reverse progression, but current noninvasive tools like magnetic resonance imaging (MRI) and ultrasound are nonspecific and detect only advanced scar tissue. We present a fibrosis-targeting, nongadolinium MRI contrast agent for sensitive and specific in vivo imaging of fibrosis. Unlike conventional methods that infer scar content via stiffness or empty dead tissue space, our agent directly binds the excess collagen substrate of the scar tissue. To synthesize the agent, we conjugated an "MRI active" manganese porphyrin to a fibrosis-targeting free-base porphyrin via the first demonstration of porphyrin photooxidative self-desulfurization of aryl thiourea linkages to stable urea or guanidine linkages. The compound exhibited high affinity for acid-soluble collagen in a new scar and significantly reduced T₁ relaxation time in collagen gels. In a mouse model of diffuse myocardial fibrosis, the fibrosis-targeting agent highlighted scar tissue that was undetected by conventional late-gadolinium MRI.