Transbronchial real-time lung tumor localization with folate receptor-targeted near-infrared molecular imaging: A proof of concept study in animal models

Objective: The diagnostic yield of bronchoscopy is not satisfactory, even with recent navigation technologies, especially for tumors located outside of the bronchial lumen. Our objective was to perform a preclinical assessment of folate receptor-targeted near-infrared imaging-guided bronchoscopy to detect peribronchial tumors.

Methods: Pafolacianine, a folate receptor-targeted molecular imaging agent, was used as a near-infrared fluorescent imaging agent. An ultra-thin composite optical fiberscope was used for laser irradiation and fluorescence imaging. Subcutaneous xenografts of KB cells in mice were used as folate receptor-positive tumors. Tumor-to-background ratio was calculated by the fluorescence intensity value of muscle tissues acquired by the ultra-thin composite optical fiberscope system and validated using a separate spectral imaging system. Ex vivo swine lungs into which pafolacianine-laden KB tumors were transplanted at various sites were used as a peribronchial tumor model.

Results: With the in vivo murine model, tumor-to-background ratio observed by ultra-thin composite optical fiberscope peaked at 24 hours after pafolacianine injection (tumor-to-background ratio: 2.56 at 0.05 mg/kg, 2.03 at 0.025 mg/kg). The fluorescence intensity ratios between KB tumors and normal mouse lung parenchyma postmortem were 6.09 at 0.05 mg/kg and 5.08 at 0.025 mg/kg. In the peribronchial tumor model, the ultra-thin composite optical fiberscope system could successfully detect fluorescence from pafolacianine-laden folate receptor-positive tumors with 0.05 mg/kg at the carina and those with 0.025 mg/kg and 0.05 mg/kg in the peripheral airway.

Conclusions: Transbronchial detection of pafolacianine-laden folate receptor-positive tumors by near-infrared imaging was feasible in ex vivo swine lungs. Further in vivo preclinical assessment is needed to confirm the feasibility of this technology.