Development of Novel Multimodal Dextran-Based Theranostic Tracers: Targeting Fibroblast Activation Protein as Proof of Concept

Project Information

POLYTROP

Grant agreement ID: 101130787

DOI

10.3030/101130787

Project closed

EC signature date 11 May 2023

Start date 1 June 2023

End date 31 May 2025

Funded under

• Widening participation and spreading excellence

Total cost

No data

EU contribution

€ 169 326,72

Coordinated by

"NATIONAL CENTER FOR SCIENTIFIC RESEARCH ""DEMOKRITOS"""
Greece

Periodic Reporting for period 1 - POLYTROP (Development of Novel Multimodal Dextran-Based Theranostic Tracers: Targeting Fibroblast Activation Protein as Proof of Concept)

Reporting period: 2023-06-01 to 2025-05-31

Summary of the context and overall objectives of the project

Cancer continues to be one of the biggest health challenges worldwide. Despite significant advances in diagnostics and therapy, there remains a critical need for more precise and less invasive tools that can both detect tumors early and help guide treatment decisions. One promising direction is the development of compounds that can perform dual roles, to detect and treat the disease simultaneously. These so-called theranostic agents are gaining increasing attention, especially in nuclear medicine.
The POLYTROP project set out to design and test a new type of such agent. The idea was to use dextran, a naturally derived, biocompatible polymer, as the base for building a modular nanoplatform. This system would be capable of carrying several functional parts: a targeting agent to direct it to the tumor, a chelator to bind radioactive metals for imaging or therapy, and a fluorescent dye to allow optical visualization. The platform was engineered to bind to the fibroblast activation protein, an enzyme commonly present in the tumor environment but not in healthy tissues.
Rather than focusing on one single application, the project aimed to create a flexible tool, a scaffold that could be adapted for different uses and targets, depending on the need. The main objective was to demonstrate a proof of concept: that this multifunctional system could be synthesized, radiolabeled with clinically relevant isotopes, and used to image tumors in living animals. If successful, this approach could form the basis for future compounds capable of not just diagnosing cancer but also helping to treat it more effectively.
The broader ambition was to bring innovation a step closer to patients. By building a platform that is chemically stable, easy to modify, and compatible with existing imaging techniques, the project hoped to support the development of more personalized approaches to cancer care. In doing so, POLYTROP also aimed to contribute to the long-term goals of the EU’s health mission, to reduce the burden of cancer across Europe.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the project, the research followed a step-by-step plan, starting in the lab and moving gradually toward testing in living systems. First, the team created a new molecule based on dextran, a sugar-like material that is safe for the body. This molecule was carefully built to include several functional parts: one to help it find cancer, one to carry radioactive elements for imaging or therapy, and another to glow under special light. Everything was connected to the same backbone, forming a small, flexible platform.
Once the molecule was ready, the next step was to attach radioactive metals to it. These radioactive parts allow doctors to see inside the body using medical scans. Four different radioactive metals were used in the study: gallium-68, copper-64, technetium-99m, and lutetium-177. The process of combining the molecule with these metals was successful, and the result was a set of new agents that could be seen clearly in imaging tests and stayed stable in the body’s fluids.
After checking the stability of these agents in test tubes, the team moved on to testing in mice that had been given small tumors similar to human cancers. These animal models allowed researchers to see where the agents went in the body after injection. The new compounds were able to find and enter tumors, and this was confirmed using special imaging cameras similar to those used in hospitals. At the same time, the compounds are also collected in the liver and kidneys, which are normal clearance organs. Because of this, the team decided not to continue with the treatment part of the study, since high uptake in these organs could limit safety.
Still, the main goal, to prove that the new platform could work for imaging cancer, was fully achieved. The compounds were easy to make, stable, and effective in highlighting tumors in live animals. On top of that, the team prepared ready-to-use kits that could help doctors or researchers prepare the compounds quickly and safely in the future.
All in all, the project showed that it’s possible to build a flexible and reliable platform that could help detect cancer. While further improvements are needed before it can be used in patients, this work sets the stage for future research and clinical development.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project took important steps beyond what is currently available in the field of cancer imaging and therapy. Many cancer tracers today are designed for a single purpose, either to image tumors or to treat them, and they often have fixed structures that are hard to adjust. The POLYTROP project introduced a new concept: a modular platform that can be easily changed, depending on the medical need. This flexibility makes it different from most tools used today.
One of the key achievements was the creation of a single molecule that can carry multiple parts, a targeting agent, radioactive metals, and even a fluorescent dye, all on the same structure. And because the base material is dextran, which is soft, safe, and easy to work with, the platform can be modified without needing to rebuild it from scratch each time. That’s a significant advantage when looking ahead to personalized medicine.
The project also proved that it is possible to label this platform with several types of radioactive elements already used in hospitals. This makes future clinical use more realistic. Another strong point was the development of a freeze-dried kit. This kind of ready-to-use format means the platform could be prepared quickly and safely in a clinical setting, which is often one of the barriers when moving from lab experiments to real-world use.
Of course, there are still some challenges to solve. For example, the compound stayed too long in the liver and kidneys. This would need to be improved before considering therapy. However, that’s one of the benefits of the design, the parts can be swapped out or adjusted. In fact, the team is already looking into replacing the Fibroblast-targeting component with others that may offer better results, especially in prostate or lung cancer. There are also efforts to make a version that works with fluorine-18, a radioactive element used widely in medical imaging, because it is easier to produce in large amounts.
To advance this work, discussions have already started with industry partners, including a pharmaceutical company interested in adapting the compound for clinical use. Intellectual property protection is being explored to support this step. With the proper support and some further research to fine-tune the design, the platform could eventually be used as a universal base for developing smart cancer tracers and future therapies.

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