Kyle D W Vollett,Anlan Hong,Wanda W Janaeska,Daryn R Browne,Hai-Ling Margaret Cheng
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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.
期刊介绍:
ACS Sensors is a peer-reviewed research journal that focuses on the dissemination of new and original knowledge in the field of sensor science, particularly those that selectively sense chemical or biological species or processes. The journal covers a broad range of topics, including but not limited to biosensors, chemical sensors, gas sensors, intracellular sensors, single molecule sensors, cell chips, and microfluidic devices. It aims to publish articles that address conceptual advances in sensing technology applicable to various types of analytes or application papers that report on the use of existing sensing concepts in new ways or for new analytes.