Bypassing Heteronuclear MRI: Metal‐Free Organosilicon Nanotracers for Background‐Free Hotspot ¹ H Imaging on Clinical Hardware

ABSTRACT

Current magnetic resonance imaging (MRI) lacks contrast agents that provide background‐free hotspot visualization while remaining compatible with standard clinical hardware and avoiding metal‐associated toxicity. Herein, we introduce a new class of metal‐free, organosilicon‐based ¹ H MRI hotspot tracers that are directly compatible with conventional experimental and clinical MRI systems. These tracers exploit the distinct chemical shift of silicon‐shielded hydrogens (∼0 ppm) spectrally resolved from the biological ¹ H background. Through architectural screening, we identified an optimized block copolymer micelle, denoted as Silicone‐Generated Hotspot Tracer (SiGHT), comprising polydimethylsiloxane (PDMS) core and a hydrophilic shell. SiGHT exhibits excellent chemical and colloidal stability and enables sensitive, background‐free ¹ H chemical shift imaging at low concentrations (< 0.5 mg mL ⁻¹ ), while being non‐cytotoxic and well tolerated in vivo. The diagnostic potential of the developed probe has been demonstrated by successful ¹ H MR hotspot visualization of tracer accumulation in 4T1 mouse tumors following intravenous administration. Importantly, we demonstrate robust tracer detection on both preclinical 7T and clinical 3T MRI scanners using standard ¹ H MR sequences and commercial coils, underscoring its translational potential. Together, these results establish organosilicon micelles as clinically relevant, metal‐free ¹ H MR hotspot tracers, opening an unexplored pathway to accessible, high‐sensitivity molecular imaging on existing MRI infrastructure.