Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6‐Tetramethylpiperidine 1‐Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo^a

Abstract

Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.

Synthesis, Stability and Relaxivity of TEEPO-Met: An Organic Radical as a Potential Tumour Targeting Contrast Agent for Magnetic Resonance Imaging

“…For example, another important medical imaging method, positron emission tomography (PET), generally applies targeting radiotracers in imaging. Also, nitroxide-based contrast agents have been attached for instance to anti-inflammatory drugs [ 20 ], folic acid [ 21 ] and glucose [ 22 , 23 ]. Quite recently, we discovered a potential tumour targeting contrast agent that consisted of a nitroxide radical connected with glucose as a targeting unit [ 23 ].…”

Pro-organic radical contrast agents (“pro-ORCAs”) for real-time MRI of pro-drug activation in biological systems

“…[37][38][39][40] Though metal-based MRI CAs have found widespread clinical utility, they continue to face safety concerns 41,42 that have led to discontinuation or withdrawal of several products. [43][44][45][46][47] Metal-free organic radical contrast agents (ORCAs) have been intensely studied in recent years to overcome the safety issues of metal-based CAs; [48][49][50][51][52][53][54][55][56][57][58] however, to our knowledge, there are no reports of theranostic ORCAs for MRIcorrelated drug release.…”

“…These inverted images were used for subsequent analysis. (B) Quantifcation of the changes in contrast over time in mice administered F, M, S, or non-cleavable control BASP (C)52 (n = 3 mice per group). Volume-averaged signal intensity across the whole tumor was calculated (see ESI † for full description).…”

A Methoxyamine‐Protecting Group for Organic Radical Battery Materials—An Alternative Approach

“…Organic radical polymers have received significant attention over the last two decades because of their redox‐active nature and found wide‐ranging application in a variety of fields including catalysis, spin probes, imaging agents, antibiofilm coatings, and most prominently of all, as electroactive materials in organic radical batteries (ORB) . The current trend towards renewable energy and increased environmental awareness has boosted research into organic‐based materials for energy applications promising safer, more powerful and environmentally friendly technologies .…”