Development of a kit for 68GA-labeling of single-domain antibody diagnostics for molecular imaging

Molecular imaging is an important tool for disease detection and following disease progression. The success of molecular imaging is based on the development of relevant tracers.
Single-domain antibodies have interesting characteristics, such as a high specificity and rapid body clearance, to perform molecular imaging. As such, sdAbs have been developed as basis for molecular imaging tracers. Particularly, sdAbs have been conjugated with a chelator for labeling with radiometals, such as gallium-68 for PET imaging.
Today, the current labeling process to couple the sdAbs with gallium-68 for clinical use remains a relatively complex process, encompassing several steps, including a purification and sterilization step. This limits the potential and clinical validation of these tracers, as the current way of working is not suitable for widespread use, such as in multi-center trials or in case of commercialization.
The solution to this issue is to have a rapid and simple labeling process, which can be achieved by working with a radiopharmaceutical kit. Such a kit ensures that all aspects concerning product quality are managed prior to performing the labeling process, so that this process can be as simple as possible with minimal steps. This, however, requires an extensive optimization of the labeling process, a high robustness and ideally, a high stability of the kit, allowing long- term storage.
To achieve these requirements, lyophilization of sdAb precursors was investigated to increase the stability, precursors were further characterized and optimized regarding the conjugation with the chelator, allowing the optimization of the labeling process to ensure a high robustness
and quality product, and lastly, an anti-radiolytic formulation was designed to prevent degradation of the tracer during and after labeling, allowing so a labeling with high starting activities.
The success in each of the points enables the kit concept for sdAb-based tracers and warrants the GMP-translation of manufacturing processes to obtain a clinical grade product, which can be used in clinical trials. As part of the translation process, optimization and upscaling of the manufacturing processes will be critical to obtain an economically viable product in case of commercialization and to allow global distribution of the kit to improve patient management around the world.