Measuring the Physiologic Properties of Oral Lesions Receiving Fractionated Photodynamic Therapy

Photodynamic therapy (PDT) can treat superficial, early‐stage disease with minimal damage to underlying tissues and without cumulative dose‐limiting toxicity. Treatment efficacy is affected by disease physiologic properties, but these properties are not routinely measured. We assessed diffuse reflectance spectroscopy (DRS) for the noninvasive, contact measurement of tissue hemoglobin oxygen saturation (StO2) and total hemoglobin concentration ([tHb]) in the premalignant or superficial microinvasive oral lesions of patients treated with 5‐aminolevulinic acid (ALA)‐PDT. Patients were enrolled on a Phase 1 study of ALA‐PDT that evaluated fluences of 50, 100, 150 or 200 J cm−2 delivered at 100 mW cm−2. To test the feasibility of incorporating DRS measurements within the illumination period, studies were performed in patients who received fractionated (two‐part) illumination that included a dark interval of 90–180 s. Using DRS, tissue oxygenation at different depths within the lesion could also be assessed. DRS could be performed concurrently with contact measurements of photosensitizer levels by fluorescence spectroscopy, but a separate noncontact fluorescence spectroscopy system provided continuous assessment of photobleaching during illumination to greater tissue depths. Results establish that the integration of DRS into PDT of early‐stage oral disease is feasible, and motivates further studies to evaluate its predictive and dosimetric value. Diffuse reflectance spectroscopy with a contact probe was employed as part of a fluorescence and reflectance spectroscopy system to measure the tissue hemoglobin oxygen saturation and hemoglobin content of lesions of premalignant or early microinvasive cancer of the oral cavity. Studies demonstrate the feasibility of incorporating these measurements into treatment with fractionated (two‐part) photodynamic therapy (PDT) using 5‐aminolevulinic acid. Patient‐specific differences in physiologic parameters were detectable at baseline and at times during and after PDT. Photobleaching of photosensitizer was measured by its fluorescence. Results establish the utility of rationally designed spectroscopy probes toward personalized dosimetry in PDT of oral disease.