Magnetic Resonance Imaging of Tumor‐Infiltrating Lymphocytes by Anti‐CD3‐Conjugated Iron Oxide Nanoparticles

Abstract Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor‐infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran‐coated superparamagnetic iron oxide nanoparticles (SPIONs‐DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs‐DEX to an anti‐CD3 monoclonal antibody via cyanogen bromide as a cross‐linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs‐DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T 2 *‐weighted and T 2 ‐weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non‐invasive assessment of TILs to identify patients eligible for immunotherapy.