COLLAGEN targeted MRI detected early lung tumors and multiorgan metastases with greater sensitivity than conventional imaging.
The experimental approach uses hProCA32.Collagen, a protein magnetic resonance imaging (MRI) contrast agent designed to bind collagen I. This extracellular matrix protein was highly expressed in the tumor microenvironment and at the invasive edges of lung adenocarcinoma with liver kinase B1 (LKB1), also known as serine threonine kinase 11 (STK11), inactivation.
Researchers evaluated hProCA32.Collagen in genetically engineered and metastatic mouse models of LKB1 mutant lung adenocarcinoma. Precision MRI using the agent detected and quantified primary lung tumors alongside metastases in the lungs, adrenal glands, and kidneys.
The technique also mapped heterogeneous collagen expression at invasive tumor margins. Multiparametric MRI and radiomics based composite scores outperformed high resolution computed tomography (CT) and MRI using a clinically approved gadolinium based contrast agent. Contrast-to-noise ratio sensitivity was threefold greater than that achieved with high resolution CT.
At 1.4 T, hProCA32.Collagen demonstrated approximately 10-fold greater r1 relaxivity than clinical gadolinium based contrast agents. This advantage decreased to approximately sixfold at 3 T, a field strength commonly used in clinical practice. Its r2 relaxivity remained approximately 13-fold higher at both 3 T and 7 T.
Analysis of tissue from 15 patients with LKB1 mutant lung adenocarcinoma identified increased collagen I expression at tumor boundaries and within the surrounding stroma. This supported collagen I as a potential imaging biomarker for primary tumors and distant metastases.
The agent demonstrated strong collagen binding, tissue penetration, serum stability, and resistance to gadolinium displacement. No blood chemistry, tissue, or organ toxicity was observed in mice during the reported assessment period. Gadolinium retention in bone, brain, and muscle was comparable to the standard contrast agent two weeks after injection.
Collagen targeted MRI could potentially support earlier diagnosis, staging, and longitudinal monitoring without ionizing radiation. Mapping collagen distribution may also provide information about tumor invasiveness, metastatic burden, and treatment response.
However, the findings remain preclinical. The study involved small animal groups, imaging analysis was not blinded, and CT was performed without a contrast agent. Further toxicology studies and clinical trials are needed to establish appropriate dosing, safety, and diagnostic performance in patients.
Reference
Li D et al. Early detection of invasive lung cancer and multiorgan metastasis by a collagen-targeted protein MRI contrast agent. Sci Adv. 2026; DOI:10.1126/sciadv.adz6815.
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