The Development and Pilot Clinical Study of CD147 Targeted Antagonistic Peptide Probe for Tumor Imaging

Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) is highly expressed in multiple malignancies and represents a potential therapeutic target. Monitoring CD147 expression noninvasively may facilitate tumor detection and guide therapeutic strategies. We developed a novel peptide‐based PET probe, [ 68 Ga]Ga‐DOTA‐AP9, and validated its pharmacokinetics and specificity in preclinical and translational uEXPLORER total‐body PET/CT studies. In preclinical models, [ 68 Ga]Ga‐DOTA‐AP9 showed high binding affinity and specific uptake in CD147‐positive A375 tumors. Encouraged by the favorable tumor‐to‐background contrast and safety profile observed in animals, [ 68 Ga]Ga‐DOTA‐AP9 total‐body PET/CT imaging was performed in eleven participants with diverse cancer types and varying CD147 expression levels. Among the eleven participants, tumor lesions showed a maximum SUV max of 10.1 at 30 min p.i., and uptake correlated strongly with CD147 (r = 0.7981, P < 0.001), MCT1 (r = 0.8555, P < 0.001), and Ki67 (r = 0.8036, P < 0.001), but not GLUT1 ( P = 0.0668). Notably, [ 68 Ga]Ga‐DOTA‐AP9 uptake more accurately reflected CD147 expression than [ 18 F]F‐FDG, with divergent uptake patterns in some lesions. These findings support that [ 68 Ga]Ga‐DOTA‐AP9 enables sensitive, noninvasive detection and quantitative assessment of CD147‐positive tumors in vivo, provides complementary diagnostic information to [ 18 F]F‐FDG PET, and holds significant potential for patient stratification, treatment selection, therapeutic response monitoring, and guiding precision oncology strategies.