In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan® in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg® and Foslip®, on FDPS response was investigated. Furthermore, FDPS was evaluated in target organs for head-and-neck PDT. Fifty-four healthy rats were intravenously injected with one of the three formulations of mTHPC at 0.15 mg kg − 1. FDPS was performed on liver, tongue, and lip. The mTHPC concentrations estimated using FDPS were correlated with the results of the subsequent harvested and chemically extracted organs. An excellent goodness of fit (R2) between FDPS and extraction was found for all formulations in the liver (R2 = 0.79). A much lower R2 between FDPS and extraction was found in lip (R2 = 0.46) and tongue (R2 = 0.10). The lower performance in lip and in particular tongue was mainly attributed to the more layered anatomical structure, which influences scattering properties and photosensitizer distribution.
The development of optical techniques for non-invasive diagnosis of cancer is an ongoing challenge to biomedical optics. For head and neck cancer we see two main fields of potential application
1) Screening for second primaries in patients with a history of oral cancer. This requires imaging techniques or an approach where a larger area can be scanned quickly.
2) Distinguishing potentially malignant visible primary lesions from benign ones. Here fiberoptic point measurements can be used as the location of the lesion is known.
This presentation will focus on point measurement techniques.
Various techniques for point measurements have been developed and investigated clinically for different applications. Differential Pathlength Spectroscopy is a recently developed fiberoptic point measurement technique that measures scattered light in a broad spectrum. Due to the specific fiberoptic geometry we measure only scattered photons that have travelled a predetermined pathlength. This allows us to analyse the spectrum mathematically and translate the measured curve into a set of parameters that are related to the microvasculature and to the intracellular morphology. DPS has been extensively evaluated on optical phantoms and tested clinically in various clinical applications.
The first measurements in biopsy proven squamous cell carcinoma showed significant changes in both vascular and morphological parameters. Measurements on thick keratinized lesions however failed to generate any vascular signatures. This is related to the sampling depth of the standard optical fibers used. Recently we developed a fiberoptic probe with a ~1 mm sampling depth. Measurements on several leukoplakias showed that with this new probe we sample just below the keratin layer and can obtain vascular signatures. The results of a first set of clinical measurements will be presented and the significance for clinical diagnostics will be discussed.
In this study, a ratiometric quantification method is developed and applied to monitor mesotetra(hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method
employs a combination of dual-wavelength excitation and dual-wavelength detection. The excitation and
detection wavelengths were selected in close to NIR. The first excitation wavelength was used to excite the
mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be substracted.
Subsequently the difference was divided by the autofluorescence. Since the method applies division of signal
with no mTHPC fluorescence, theory suggests on linear dependency of the method on photosensitizer
concentration.
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