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

## TL;DR

A new ratiometric fluorescent drug is developed for treating and monitoring ovarian cancer metastasis using low doses and real-time imaging.

## Contribution

The novel n501-CYMMAF theranostic agent combines treatment and response monitoring for ovarian metastasis.

## Key findings

- n501-CYMMAF shows strong target affinity with an EC50 of 1.17 nm.
- The drug enables in situ tracking of treatment-evading metastatic cells.
- It offers a platform for precision metastasis management with dual therapeutic and imaging functions.

## Abstract

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 (EC50(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.

In vivo optical imaging enhances antibody‐drug conjugate (ADC) optimization by enabling real‐time monitoring of stimulus‐responsive drug behavior. We report n501‐CYMMAF, a ratiometric theranostic with strong target affinity and low‐dose efficacy for ovarian metastasis. Its dual therapeutic and imaging functions allow in‐situ tracking of treatment‐evading cells, offering insights into recurrence and treatment endpoints. n501‐CYMMAF exemplifies next‐generation precision metastasis theranostics.