# Roadmap for the accelerated development and clinical translation of fluorescent tracers: Adalimumab-680LT as a proof of concept

## TL;DR

This paper introduces a faster, standardized process for developing fluorescent tracers, demonstrated with adalimumab-680LT for clinical trials in inflammatory bowel disease.

## Contribution

A novel accelerated roadmap for fluorescent tracer development, reducing clinical translation time by 40%.

## Key findings

- Adalimumab-680LT was developed under cGMP conditions with 82.8% label efficiency.
- Stability of adalimumab-680LT was confirmed for up to 24 months.
- Phase I/II clinical trials using adalimumab-680LT are currently ongoing.

## Abstract

Fluorescence molecular imaging (FMI), using fluorescent labelled antibodies, can provide insight into local drug distribution, identification of target cells and target engagement. However, clinical translation of novel fluorescent tracers is hampered by their extensive and time-consuming development process, highlighting the need for an accelerated and standardised process. This study presents a general roadmap for accelerated fluorescent tracer development and clinical translation and compares it to the original development process. The accelerated development process introduced feasibility testing, to minimize small-scale experiments, while the introduction of lab runs, combined with a technology transfer, allowed for earlier collection of stability data, further accelerating the development process. Accordingly, adalimumab-680LT was developed as a proof of concept using this accelerated roadmap. Development was mainly performed using labelling parameters, analytical methods, and QC-tests of previously developed tracers and building upon this experience. Adalimumab was successfully conjugated to IRDye 680LT under current Good Manufacturing Practice (cGMP) conditions. Feasibility testing and small-scale experiments yielded a robust and cGMP-compliant production process, with label efficiencies of 82.8 ± 2.9%. Short- and long-term stability was demonstrated in stability studies up to 24 months, with a target binding affinity between 58 and 86%, and a monomer concentration between 0.97 and 1.05 mg/mL. Following the accelerated roadmap, adalimumab-680LT could already be used in phase I/II clinical trials in humans 12 months after the first experiments, a time reduction of 40%, or 8 months. From this point forward, the described roadmap can be applied to develop novel clinical-grade antibody-based fluorescent tracers, saving valuable time and resources.

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•Fluorescent tracer development must be accelerated and standardised.•The novel roadmap enables translation from idea to clinical trial within 12 months.•Adalimumab-680LT was developed for fluorescent imaging in inflammatory bowel disease.•Stability of adalimumab-680LT was confirmed up to 24 months after production.•The first phase I/II clinical trials with adalimumab-680LT are currently ongoing.

Fluorescent tracer development must be accelerated and standardised.

The novel roadmap enables translation from idea to clinical trial within 12 months.

Adalimumab-680LT was developed for fluorescent imaging in inflammatory bowel disease.

Stability of adalimumab-680LT was confirmed up to 24 months after production.

The first phase I/II clinical trials with adalimumab-680LT are currently ongoing.