Gram‐Scale Synthesis of Hafnium‐Rich Carbon Dots for Preclinical Computed Tomography Imaging Across Various Systems

ABSTRACT Hafnium (Hf) has emerged as a promising element for next‐generation computed tomography (CT) contrast agents owing to its high X‐ray attenuation coefficient and favorable biocompatibility. However, scalable synthesis of Hf‐based imaging probes with sufficiently high metal content for large‐animal preclinical studies remains challenging. Here, we report a facile air‐assisted pyrolysis strategy for the gram‐scale synthesis of Hf‐rich carbon dots (Hf‐rCDs). The resulting Hf‐rCDs exhibit a high Hf content (40.7%), robust batch productivity (>2 g per batch), ultra‐small hydrodynamic size (∼3.2 nm), excellent aqueous solubility (up to 600 mg mL − 1 ; 244 mg Hf mL − 1 ), and superior X‐ray attenuation performance. Importantly, Hf‐rCDs demonstrate rapid renal clearance within 2 h post‐injection, supporting a favorable biosafety profile. In vivo CT imaging reveals outstanding contrast enhancement across multiple physiological systems, including the circulatory, urinary, gastrointestinal, and lymphatic systems. Notably, Hf‐rCDs enable high‐resolution visualization of cervical vasculature in swine, highlighting their strong translational potential. Collectively, these results establish Hf‐rCDs as a compelling alternative to conventional iodine‐based contrast agents for advanced CT imaging.