Early detection of invasive lung cancer and multiorgan metastasis by a collagen-targeted protein MRI contrast agent

Lung cancer with multiorgan metastasis remains the leading cause of cancer death. Current CT imaging and biopsy are suboptimal for detecting early tumors or subclinical metastases. We address this gap using LUAD with LKB1/STK11 inactivation, which alters collagen via focal adhesion kinase activation. Collagen I overexpression in the tumor microenvironment and invasive edge was identified as a biomarker. We developed hProCA32.Collagen, a protein MRI contrast agent targeting collagen I, which exhibits 10-fold higher relaxivity than clinical GBCAs, with strong Gd 3+ binding, high stability, and low toxicity risk. Precision MRI with hProCA32.Collagen enables early, noninvasive detection and quantification of lung tumors and metastases with improved contrast, outperforming CT and standard MRI. This is a demonstration of simultaneous MRI detection of primary tumors and metastases in the lung and adrenal glands, with collagen mapping. This approach offers a radiation-free tool for early diagnosis, staging, and monitoring in LUAD.