February 23, 2023

Personalized Precision Medicine Using Folate Radiotheragnostics for Selective Targeting of the Tumor-associated Folate Receptor-α

7th Call, iDoc

Short Summary

This project focuses on the investigation of the folate receptor-alpha (FRα) as a tumor marker to be exploited for targeted radionuclide therapy using folate-based radiopharmaceuticals. In a first step, we will investigate the FRα expression profile in specific tumor types. In a second step, we plan to develop radioconjugates with an optimized design to enable high and specific tumor accumulation but negligible uptake in normal tissue. In an ideal case, the project would deliver the basis for a clinical translation of a new folate radioconjugate to treat patients suffering from a tumor type known to express the FRα.

Goals

The aim of this project is to identify, characterize and investigate a large number of cancer (sub)types for the expression levels and profile of the FRα. High-throughput tissue microarray screening for FRα expression will be performed at the University Hospital Zurich using state-of the art methodologies. Information about the FRα expression on a variety of tumor types will be essential in view of our goal to develop FR-targeted radionuclide therapy. At the Center for Radiopharmaceutical Sciences at Paul Scherrer Institute (Villigen-PSI), the design of FRα-targeting folate radioconjugates will be optimized to reduce undesired kidney retention and allow their use for therapeutic purposes. The project should form the basis for a new theragnostic concept with the long-term goal to provide a valid approach for personalized precision medicine in oncology.

Significance

It is exspected that by having finalized this project, a clear-cut decision can be drawn on whether (i) the FRα is a valid tumor-associated marker for the development of tumor-targeted therapies and (ii) whether the newly developed FRα-targeted radiopharmaceuticals have the potential for future clinical translation to treat patients with advanced cancer diseases.

Background

Despite the current progress in cancer research, there is still a lack of efficient treatment options for patients with cancer at metastasized stage. Among the most promising concepts is “targeted radionuclide therapy” using tumor-specific carriers that deliver therapeutic radionuclides to the malignant cells (radiopharmaceuticals). While this concept is clinically applied for prostate cancer, there is an urgent need to develop radiopharmaceuticals for the treatment of other cancer types. The FRα is an interesting target in this regard as it is expressed on a variety of cancer diseases and can be targeted with folate radioconjugates.