A system for interstitial photodynamic therapy with ␦-aminolaevulinic acid and multiple optical fibers has been developed. The system enables photodynamic treatment of large embedded tumor volumes and utilizes real-time measurements to allow on-line dosimetry. Important parameters such as light fluence rate, sensitizer fluorescence intensity, and changes in local blood oxygen saturation are measured with the same fibers that deliver the therapeutic light. Data from the first clinical treatments on nodular basal cell carcinomas indicate a major treatment-induced light absorption increase, rapid sensitizer photobleaching, and a relatively constant global tissue oxygen saturation level during the treatment.

Abstract.A system for interstitial photodynamic therapy is used in the treatment of thick skin tumors. The system allows simultaneous measurements of light fluence rate, sensitizer fluorescence, and tissue oxygen saturation by using the same fibers as for therapeutic light delivery. Results from ten tumor treatments using ␦-aminolevulinic acid ͑ALA͒-induced protoporphyrin IX show a significant, treatmentinduced increase in tissue absorption at the therapeutic wavelength, and rapid sensitizer photobleaching. The changes in oxy-and deoxyhemoglobin content are monitored by means of near-infrared spectroscopy, revealing a varying tissue oxygenation and significant changes in blood volume during treatment. These changes are consistent with the temporal profiles of the light fluence rate at the therapeutic wavelength actually measured. We therefore propose the observed absorption increase to be due to treatment-induced deoxygenation in combination with changes in blood concentration within the treated volume. A higher rate of initial photobleaching is found to correlate with a less pronounced increase in tissue absorption. Based on the measured signals, we propose how real-time treatment supervision and feedback can be implemented. Simultaneous study of the fluence rate, sensitizer fluorescence, and local tissue oxygen saturation level may contribute to the understanding of the threshold dose for photodynamic therapy. © 2006 Society of Photo-Optical Instrumentation Engineers.

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Kinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid.Pålsson, Sara; Gustafsson, Lotta; Bendsöe, Niels; Soto Thompson, Marcelo; AnderssonEngels, Stefan; Svanberg, Katarina Kinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid. British Journal of Dermatology, 148(6), 1179 -1188 . DOI: 10.1046 /j.1365 -2133 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal PhotobiologyKinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid SummaryBackground Photodynamic therapy (PDT) is a local treatment modality with increasing indications for various malignant and non malignant diseases. The treatment parameters have not yet been optimized as there is a need for a better understanding of the process. The skin is an important target and serves as a good model for monitoring and evaluating the interaction of light with biological tissue. Objectives The tissue perfusion and the temperature of basal cell carcinomas were measured in connection with PDT in order to investigate the biological mechanisms involved. Methods An infrared camera was used during the treatment to measure skin temperature and a laser Doppler perfusion imaging device was used to image the superficial perfusion before and after treatment. Six hours after topical application of 5-aminolaevulinic acid (ALA) or methyl esterified ALA (ALA-ME), 38 basal cell carcinomas were treated using light from a diode laser at 633 nm. Results In the lesions, the perfusion immediately after PDT was similar to that before PDT. One hour after the treatment the perfusion in the lesion was increased 50% compared with before PDT. However, in the skin surrounding the lesions the perfusion was doubled immediately after PDT and was still increasing 1 h after treatment. A temperature increase in the lesions of about 1-3°C was observed for light fluence rates of 100-150 mW cm

ABSTRACT:Various optical techniques were used to investigate relevant parameters involved in photodynamic therapy (PDT) of human basal cell carcinomas (BCCs). The aim of the study was to compare the diagnostic and therapeutic outcome when using topically applied methyl-esterified -aminolevulinic acid (ALA-ME) and -aminolevulinic acid (ALA). A total of 35 pathologically verified BCCs in 14 patients were investigated. A diode laser, emitting continuous light at 633 nm, was used to induce PDT. The diagnostic measurements were performed before, during, and after PDT. Laser-induced fluorescence (LIF) was used to monitor the build-up of the ALA/ALA-ME-induced protoporphyrin IX (PpIX). The superficial tissue perfusion was measured with laser-Doppler perfusion imaging (LDPI) and the temperature of the lesion and the surrounding tissue was imaged with an IR-camera. A clear demarcation between the lesion and the normal skin was detected with LIF before the treatment for both PpIX precursors. The fluorescence measurements suggest that PpIX builds up to a higher degree and more selectively in the tumour following ALA-ME as compared to ALA. The LDPI measurements indicate a local transient restriction in blood perfusion immediately post-PDT. The measurement with the IR-camera revealed a temperature rise of about 1-2°C during the treatment.