Project title: Developing a functional in vitro model to investigate renal toxicity of radionuclide therapy agents

Project Description:

Dr. Kossatz and her team aims to establish a new cell-based technology that could accelerate discovery and optimization of radiopharmaceuticals for NET treatment. High kidney uptake and retention of therapeutic radiopeptides is currently a major factor that limits clinical translation and application of peptide receptor radionuclide therapy (PRRT). Their goal is to establish an in vitro assay system using functional proximal tubule epithelial cells that can predict in vivo kidney uptake and retention of radiopharmaceuticals.

What critical NET problem will you try to solve through your research?

High kidney uptake and retention of therapeutic radiopeptides is currently a major factor that limits clinical translation and application of peptide receptor radionuclide therapy (PRRT). An important bottleneck in the development of new radiopharmaceuticals is not their synthesis, but the biological evaluation of each new compound. While many characteristics can be efficiently screened in vitro to assess their potential for in vivo studies and translation, kidney uptake and retention are crucial aspects of radiopharmaceuticals that cannot yet be evaluated in vitro.

Why is this important?

Currently, renal uptake and retention of new radiopharmaceuticals is only evaluated once a ligand reaches the in vivo level, which does not allow for high-throughput screening to identify novel ligands with a suitable renal uptake profile for PRRT. This results in a limited number of radiopharmaceuticals that can be screened in vivo, which in turn contributes to the lack of a clear understanding of kidney uptake and retention of radiopharmaceuticals and how they can be controlled. Furthermore, it limits the ability for broad testing of available and novel approaches for renal protection.

What will you do as part of this research project?

Dr. Kossatz’s goal is to establish a cell-based in vitro assay system that can predict the uptake and retention of novel radiopharmaceuticals via proximal epithelial tubule cells and therefore enhance the identification of novel ligands with potential for clinical translation. They will also explore if the model is suitable to investigate the mechanisms of renal uptake and retention of radiopharmaceuticals as well as renal injury at the cellular level.

How might your research improve the diagnosis and/or treatment of NETs? 

Having an improved preclinical pipeline for radioligand development and renal protection will likely result in the discovery of enhanced PRRT ligands for existing and novel NET biomarkers and enable their clinical translation. Overall, NET patients would benefit from having access to additional radiopharmaceuticals for efficient treatment at early and late disease stages and for different NET types.

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