Background: Rapid and precise imaging is critical for timely therapeutic interventions that minimize brain damage in ischemic stroke. Conventional iodine-based contrast agents (ICA) enhance vascular visibility but fail to delineate cellular and molecular alterations in ischemic tissues. To bridge this gap, we developed Transferrin-Conjugated Iodine Contrast Agent Liposomes (TICA), a novel targeted agent designed to bind transferrin receptors upregulated in ischemic brain regions.

Methods: TICA was synthesized to target transferrin receptors overexpressed during ischemic injury. Its efficacy was evaluated using a comprehensive set of imaging and histological techniques in a rat Middle Cerebral Artery Occlusion (MCAO) model. Serial Computed Tomography (CT) imaging was conducted to evaluate the clarity and extent of ischemic regions. Triphenyltetrazolium chloride (TTC) staining was performed to verify the extent of ischemic damage, while immunohistochemical analysis quantified transferrin receptor expression in brain tissue. Additionally, Terminal deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) staining was employed to quantify cellular apoptosis in ischemic regions. Results obtained with TICA were compared against those from standard ICA to demonstrate the enhanced capability of TICA in identifying and characterizing ischemic damage.

Results: Initial CT imaging demonstrated that TICA provided clearer and more comprehensive visualization of ischemic regions than ICA. Longitudinal imaging further showed that TICA consistently delineated ischemic areas with greater spatial precision, findings corroborated by histopathological analysis. Collectively, these findings indicate that TICA improves both the initial identification and temporal monitoring of ischemic injury.

Conclusion: TICA represents a significant advancement in ischemic stroke imaging by offering a targeted, pathophysiology-aligned visualization of ischemic tissue. Its application improves diagnostic accuracy and may enhance treatment planning, potentially improving clinical outcomes in stroke management.