Executive Summary : | Early detection of cancerous tissue is of crucial importance for effective treatment. Magnetic resonance imaging (MRI) has been extensively employed as an invaluable imaging technology for disease diagnosis and therapy monitoring. MRI does not use ionizing radiation, unlike other imaging procedures, such as X-ray computed tomography (CT), and is hence non-harmful to humans. 1H MRI has been the predominant mode in clinical scans. However, limited sensitivity (due to the abundance of H2O molecules in the body generating strong background signals) and low contrast (due to similar proton relaxation times Iin different tissues) has limited its applicability. This led to the recent research thrust towards 19F MRI which offers some advantages (over other NMR-active nuclei such as 13C, 15N and 31P) such as high sensitivity and zero confounding 19F background signal within the body (due to its absence in the human body). 19F MRI may provide additional information which may complements those obtained from 1H MRI and thus is having potential applications in emerging areas, including cell labeling, cell tracking, and so on. However, commonly employed 19F contrast agents such as perfluorocarbons (PFCs) and perfluoropolyether (PFPEs) suffer from non-biodegradability and bioaccumulation and low sensitivity due to their hydrophobicity and limited methods of functionalization. “Smart” pH responsive 19F MRI contrast agents sensitive to changes in environmental pH is expected to be useful for selective imaging of cancer tissues because of the variation of pH in normal tissue (physiological pH of 7.4) and cancer tissue (slightly acidic extracellular pH (6.5–6.9). However, careful choice of the fluorinated moiety and pH responsive segment is required to develop a pH responsive 19F contrast agent which is also biodegradable and the technology must be further refined before it can replace conventional imaging methods. In order to overcome the existing gaps, we plan to develop a fluorine-containing contrast agent for 19F MRI based on multi-arm star S-S crosslinked polymer network bearing a pH responsive [poly(l-histidine methacrylamide), PHisMAM or poly(l-lysine methacrylamide), PLysMAM] segment and a hydrophobic fluorinated [2,2,2-Trifluoroethyl acrylate, PTFEA or poly(1,1,1,3,3,3-Hexafluoroisopropyl acrylate), PHFiPA] segment that provide the potential for biodegradation of the S-S crosslinked network by reducing agents such as glutathione (GSH). Due to their amphiphilic nature, the polymer is expected to undergo spontaneous self-assembly in water to form stable micelles, having a fluorine-rich core that provides a strong signal for MRI examinations. Additionally, as extracellular pH of cancerous tissues are slightly acidic (6.5–6.9) compared to a normal tissue, it is envisaged that these cancerous cells may be detected through selective imaging using the developed pH responsive 19F MRI contrast agent. |