NIR Ratiometric Fluorescent Antibody‐Drug Conjugate for Metastatic Ovarian Cancer Theranostics and Treatment Response Monitoring

In vivo optical imaging advances antibody-drug conjugate (ADC) optimization by enabling real-time monitoring of biological stimulus-responsive drug behavior. Ratiometric probes, incorporating orthogonal wavelength-encoded multicolor detection and stimuli-cleavable linkages, are preferred over single-color strategies. Here, the synthesis of n501-CYMMAF (cyanine-decorated Monomethylauristatin F) is described as a novel ratiometric theranostic agent for dual efficacy in ovarian metastasis treatment and in situ treatment response monitoring. With low-dose administration (2.5 mg kg^-1), exceptional target affinity (EC_{50(n501-CYMMAF)} = 1.17 nm), and favorable biosafety (delivery to tumor-parts only), n501-CYMMAF enables experimental verification of treatment-evading metastatic cell populations through in situ fluorescent tracking, providing crucial insights into tumor recurrence pathways and judgement of treatment terminal point. In general, n501-CYMMAF represents a prototype for next-generation smart theranostics, integrating treatment and endpoint assessment to offer a platform for precision metastasis management.