Monitoring of hexyl 5-aminolevulinate-induced photodynamic therapy in rat bladder cancer by optical spectroscopy

Abstract

Monitoring of the tissue response to photodynamic therapy (PDT) can provide important information to help optimize treatment variables such as drug and light dose, and possibly predict treatment outcome. A urinary bladder cancer cell line (AY-27) was used to induce orthotopic transitional cell carcinomas (TCC) in female Fischer rats, and hexyl 5-aminolevulinate (HAL, 8 mM, 1 h)-induced PDT was performed on day 14 after instillation of the cancer cells (20 J/cm(2) fluence at 635 nm). In vivo optical reflectance and fluorescence spectra were recorded from bladders before and after laser treatment with a fiberoptic probe. Calculated fluorescence bleaching and oxygen saturation in the bladder wall were examined and correlated to histology results. Reflectance spectra were analyzed using a three-layer optical photon transport model. Animals with TCC treated with PDT showed a clear treatment response; decreased tissue oxygenation and protoporphyrin IX (PpIX) fluorescence photobleaching were observed. Histology demonstrated that 3 of 6 animals with treatment had no sign of the tumor 7 days after PDT treatment. The other 3 animals had significantly reduced the tumor size. The most treatment-responsive animals had the highest PpIX fluorescence prior to light irradiation. Thus, optical spectroscopy can provide useful information for PDT. The model has proved to be very suitable for bladder cancer studies.

Fluorescence and Treatment Light Monitoring for Interstitial Photodynamic Therapy

“…In an earlier investigation, Larsen et al . had found met‐Hb formation in a rat bladder tumor model, in which some of the animals the relative contribution to overall oxy‐Hb was up to 40% after 5‐ALA‐based PDT. Interestingly, met‐Hb has a broad absorption peak at ca.…”

Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome

“…Diffuse optical spectroscopy (DOS) can be used to probe biological tissue for its optical properties such as absorption and scattering coefficients. DOS has been used to measure the tissue oxygenated hemoglobin (HbO 2 ), deoxygenated hemoglobin (Hb), total hemoglobin concentration (THC), and oxygen saturation (StO 2 ) levels of PDT-treated tumors [28–30, 32]. Diffuse correlation spectroscopy (DCS) allows us to measure the relative blood flow (rBF) in a tumor by using the autocorrelation function of fluctuating light intensities to calculate the average flow rate of scattering particles [28–29, 33].…”

Ruthenium porphyrin-induced photodamage in bladder cancer cells

“…6). The cell line AY27 is an appropriate model for PDT study of bladder cancer, shown by previous studies, using hexylaminolevulinate (HAL) [33,39] and photochemical internalization (PCI) (see Ref. [40]).…”

“…Preclinical studies also play an important role in this aspect [32]. Investigations on bladdercancer cell lines is a natural first step to determine the properties of newly developed drugs and to test various treatment strategies [6,[33][34][35][36].…”