Phosphorus- and fluorine-containing hydrophilic polymers: innovative probes for combined 1H/31P/19F magnetic resonance imaging

Lucie Kracíková
Lecture of the lecture cycle
24.10.2024 11:00, Lecture room A

A novel set of bio-responsive polymer probes has been developed, enabling multimodal imaging capabilities through 1H/31P/19F magnetic resonance (MR) techniques. This innovation encompasses three distinct categories of polymer probes, each incorporating different X-nuclei or (super)paramagnetic compounds. The first category features a phosphorus-containing zwitterionic polymer, which serves as a metal-free 31P MRI probe. This probe exhibits a remarkably high-intensity 31P MR signal, clearly distinguishable from biological background noise, due to the incorporation of a naturally rare phosphorothioate group (P=S). Notably, this polymer undergoes oxidation-induced structural changes in the presence of reactive oxygen species, allowing for potential applications in detecting tumors or areas of inflammation. The second category consists of conjugates of the phosphorus-containing zwitterionic polymer with either superparamagnetic γ-Fe2O3 nanoparticles or paramagnetic Fe3+ ions, functioning as dual 1H/31P contrast agents/probes. While the contrast agents incorporating low-molecular-weight Fe3+ ions displayed satisfactory imaging capabilities with both 1H and 31P MR despite their relatively short relaxation times, those consisting of γ-Fe2O3 nanoparticles were impossible to visualize using 31P MR due to their extremely short relaxation times. The third category includes water-soluble copolymers that contain both phosphorus and fluorine atoms, enabling dual 31P/19F MRI. Specifically, these are zwitterionic phosphopolymers bearing fluorine-containing moieties such as 5-fluorouracil-1-yl acetic acid or 3,5-bis(trifluoromethyl)benzylamine. These probes exhibit optimal relaxation times for both 31P and 19F, facilitating clear visualization through two independent MR modalities. Furthermore, the polymer probe containing the 5-fluorouracil residue not only serves as a probe but may also function as an anticancer prodrug. All synthesized polymer contrast agent/probes, which incorporate phosphorus, fluorine, and/or iron, have been successfully visualized using three distinct MR imaging modalities—31P, 19F, and 1H MR. Additionally, the probes featuring P=S groups demonstrate antioxidant properties, positioning them as sensitive MR sensors for oxidative stress. The 5-fluorouracil-conjugated probe further emphasizes the potential for applications in cancer diagnosis and treatment.

The lecture is presented in English