Lessons learned in application driven imaging agent design for image-guided surgery

European Journal of Nuclear Medicine and Molecular Imaging, vol. 51, pp. 3040–3054

Abstract

To meet the growing demand for intraoperative molecular imaging, the development of compatible imaging agents plays a crucial role. Given the unique requirements of surgical applications compared to diagnostics and therapy, maximizing translational potential necessitates distinctive imaging agent designs. For effective surgical guidance, exogenous signatures are essential and are achievable through a diverse range of imaging labels such as (radio)isotopes, fluorescent dyes, or combinations thereof. To achieve optimal in vivo utility a balanced molecular design of the tracer as a whole is required, which ensures a harmonious effect of the imaging label with the affinity and specificity (e.g., pharmacokinetics) of a pharmacophore/targeting moiety. This review outlines common design strategies and the effects of refinements in the molecular imaging agent design on the agent's pharmacological profile. This includes the optimization of affinity, pharmacokinetics (including serum binding and target mediated background), biological clearance route, the achievable signal intensity, and the effect of dosing hereon.

Authors 4

1. Tessa Buckle Aachen Interventional Molecular Imaging Laboratory

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands

2. Daphne D. D. Rietbergen Aachen Interventional Molecular Imaging Laboratory Section Nuclear Medicine Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Interventional Molecular Imaging Laboratory, Leiden University Medical Center, Leiden, The Netherlands

   Section Nuclear Medicine, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands

3. Berlinda J. de Wit–van der Veen

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

4. Margret Schottelius corresponding

   Centre Hospitalier Universitaire Vaudois · Swiss Cancer Center Léman · University of Lausanne

   Affiliation as printed

   Agora, pôle de recherche sur le cancer, Lausanne, Switzerland. margret.schottelius@chuv.ch

   Translational Radiopharmaceutical Sciences, Department of Nuclear Medicine and Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Rue du Bugnon 25A, Agora, Lausanne, CH-1011, Switzerland. margret.schottelius@chuv.ch

   Translational Radiopharmaceutical Sciences, Department of Nuclear Medicine and Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, Rue du Bugnon 25A, Agora, Lausanne, CH-1011, Switzerland