SBIR-STTR Award

Technique will be developed to measure the concentration of a fluorophore in vivo, from detection of the fluorescence to reflected light ratio using a specialized fiber optic bundle which limits the probed tissue volume. This technique will allow real-time in vivo optical biopsy of any fluorophores from a tissue. By limiting the probe (fiber optic) area on the tissue to smaller than the typical scattering length, the detected signal is insensitive to the tissue's natural absorption characteristics, and is proportional to only the fluorophore concentration. Then by dividing the fluorescent light by the reflected light, the variations in scattering coefficient are eliminated from the measurement. For example, the fluorescence signal from dark and light pigmented skin should be equal, for equal concentrations of fluorophore. In photodynamic therapy, it can be used to measure the uptake of photosensitizer within tissues, and may eventually replace time consuming tissue extraction methods which are currently used. A special fiber optic bundle will be created which samples a number of small spots on the tissue, and integrates the signals into a single measurement. This process retains the insensitivity to the tissue type while allowing lower light intensities to be used. PROPOSED COMMERCIAL APPLICATIONS: The fiber optic based system outlined in this proposal would be an extremely useful tool for all clinics involved in photodynamic therapy research and clinical trials. Essentially all of these labs need to quantitate the photosensitizer uptake in tissue for accurate treatment planning. Current methods are time consuming and expensive. Beyond photodynamic therapy, this device would also have potential to provide pharmacokinetic studies of fluorescent tracer drugs injected in vivo.

The efficacy and safety of photodynamic therapy (PDT) depends on an understanding of photosensitizer and light biology and dosimetry. Therefore, the ability to accurately determine photosensitizer levels in tumors and at-risk normal tissues is of utmost importance. The goal of this work is to develop and test a prototype system for fluorescence based measurement of photosensitizer uptake in tissue, to improve photodynamic therapy (PDT) dosimetry. The fiber optic system is designed to quantify photosensitizer concentration by detecting a fluorescence intensity signal which minimizes the impact of the tissue optical properties. The bundle is also designed to maximize the signal intensity, allowing quantitation of low concentrations of photosensitizers. Specialized designs have been developed for tissue surface measurement, interstitial measurement and sampling of drawn blood samples. The system is flexible enough to measure either porphyrin-based or phthalocyanine-based photosensitizers, and will specifically be tested in aminolevulinic acid-induced protoporphyrin IX (ALA - PpIX), Photofrin and aluminum disuiphonated phthalocynanine. The system design will be tested in three specific applications where PDT can be successfully commercialized, including (i) veterinary animal tumor therapy, (ii) research in experimental animal tumors, and (iii) adjuvant therapy for human brain tumors after resection. In order to successfully evaluate the system in these different PDT markets, prototype systems will be developed and tested in academic research labs at Dartmouth Medical School and the University of Toronto. The tests will (i) determine how robust the design is, (ii) determine if this dosimetry method improves PDT treatment outcome and (iii) demonstrate safety in human use, prior to commercial development