Enabling point of care optical diagnostics and treatment of oral lesions in resource-limited settings: preclinical development and evaluation of a low-cost theranostic intraoral device for image-guided photodynamic therapy

Significance: Oral squamous cell carcinoma (OSCC) is exceedingly prevalent and deadly in South Asia, especially the Indian subcontinent, affecting 15 out of every 100,000 people and claiming over 70,000 lives annually. This problem is compounded by inadequate medical infrastructure for screening and cancer care, especially in rural areas. Aim: We sought to build and evaluate a theranostic, low-cost, intraoral device to enable simultaneous multichannel optical imaging and photodynamic therapy (PDT) for the detection and treatment of early oral cancer. Approach: The system’s performance was assessed using buccal mucosal tissue phantoms containing protoporphyrin IX (PpIX), as well as OSCC in vitro tumor models photosensitized with 5-aminolevulinic acid (ALA)-induced PpIX. A murine xenograft model consisting of athymic nude mice implanted with TR146 OSCC cells was used to evaluate the capability of the device to function as a PDT light source with integrated monitoring of PpIX photobleaching as a dosimetry reporter. Experiments were complemented by Monte Carlo modeling of light delivery. Results: In tissue phantoms the intraoral device reported a linear correlation up to 50μM PpIX concentration and the extent of photobleaching increased with increasing light dose up to 100J/cm². PpIX fluorescence contrast was found to improve by using ratiometric analysis of PpIX (red) and autofluorescence (green) fluorescence signals. In mouse models that received PDT treatment via the intraoral device, tumor volume decreased significantly, with histological analysis showing necrosis extending to a depth of 3.0 to 3.5 mm after PDT and consistent with Monte Carlo modeling of light delivery. Conclusion: A compact, handheld, and low-cost intraoral device with a dental camera form factor is able to carry out simultaneous multichannel white light and fluorescence imaging and image-guided PDT light delivery. The ability to quantify the extent of photobleaching as a dosimetry surrogate points to the potential for real-time treatment monitoring with the same hardware.