Sebastiaan A. H. J. de Visscher

Epithelioid sarcoma : Still an only surgically curable disease

Epithelioid sarcoma is a rare soft tissue sarcoma with a known high propensity for locoregional recurrence and distant metastases. The clinical behavior and prognostic factors that influence the survival of patients with epithelioid sarcoma were studied.

mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers : Development of a new method

Interstitial photodynamic therapy (iPDT) can be an option in the management of locally recurrent base of tongue cancer after (chemo)radiation treatment. The purpose of the current study was to develop a technique to implant light sources into the tumor tissue.

Fluorescence localization and kinetics of mTHPC and liposomal formulations of mTHPC in the window-chamber tumor model

Foslip® and Fospeg® are liposomal formulations of the photosensitizer mTHPC, intended for use in Photodynamic Therapy (PDT) of malignancies. Foslip consists of mTHPC encapsulated in conventional liposomes, Fospeg consists of mTHPC encapsulated in pegylated liposomes. Possible differences in tumor fluorescence and vasculature kinetics between Foslip, Fospeg, and Foscan® were studied using the rat window‐chamber model.

Photochemical internalization (PCI)-mediated enhancement of bleomycin cytotoxicity by liposomal mTHPC formulations in human head and neck cancer cells.

Photodynamic therapy (PDT) with photosensitizers that locate in endocytic vesicles of cancer cells can be exploited to promote the intracellular release of anticancer drugs entrapped in endolysosomal vesicles. This new approach is commonly referred to as Photochemical Internalization (PCI). Here we report on the PCI effects of three different formulations (Foscan, Foslip, and Fospeg) of the clinically approved photosensitizer, meta‐tetrahydroxyphenyl chlorin (mTHPC) on the anticancer drug bleomycin (BLM) in the head and neck cancer cell lines.

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: Influence of photosensitizer formulation and tissue location

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 (R(2)) between FDPS and extraction was found for all formulations in the liver (R(2)=0.79). A much lower R(2) between FDPS and extraction was found in lip (R(2)=0.46) and tongue (R(2)=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.

Fluorescence kinetics of Foscan, Fospeg and Foslip in the window-chamber model

Introduction Foslip and Fospeg are new formulations of the photosensitzer m-THPC, intended for use in Photodynamic Therapy (PDT) of malignancies. Foslip is m-THPC bound to conventional liposomes, Fospeg consists of m-THPC bound to pegylated liposomes. Possible differences in tumour-fluorescence and vasculature kinetics between Foslip, Fospeg and Foscan were studied using the rat window-chamber model.

Localization of Liposomal mTHPC Formulations within Normal Epithelium, Dysplastic Tissue, and Carcinoma of Oral Epithelium in the 4NQO-Carcinogenesis Rat Model

Foslip and Fospeg are liposomal formulations of the photosensitizer mTHPC (Foscan), which is used for photodynamic therapy (PDT) of malignancies. Literature suggests that liposomal mTHPC formulations have better properties and increased tumor uptake compared to Foscan. To investigate this, we used the 4NQO‐induced carcinogen model to compare the localization of the different mTHPC formulations within normal, precancerous, and cancerous tissue. In contrast to xenograft models, the 4NQO model closely mimics the carcinogenesis of human oral dysplasia.

Non-invasive measurement of photosensitiser concentration using fluorescence differential path-length spectroscopy: validation for different liposomal formulations of m-THPC: Foscan, Foslip and Fospeg

As previously described, Fluorescence differential path length spectroscopy (FPDS) can determine chromophore concentrations non-invasively after injection with m-THPC (Foscan) in the rat liver [1]. Our first aim is to validate FDPS for two other, liposomal formulations of m-THPC; pegylated liposomes (Fospeg) and conventionel liposomes (Foslip), and compare them to Foscan. As a proof of principle we use the highly vascularised, optically homogenous liver of the rat [1] Validation of the FDPS-measurements was done by chemical extraction of the same liver [2]. Our second aim is to validate FDPS measurements of the tongue, which is optically less homogenous, but clinically more relevant. After successful validation in both liver and tongue tissue, the pharmacokinetic-profile in other tissue types could be assessed by FDPS alone. Therefore, FDPS can lower the need for labour-intensive chemical extraction. Fifty-four male Wistar rats were intravenously injected with one of the three formulations of m-THPC; eighteen rats for each formulation. All rats were injected with 0.15 mg kg m-THPC. FDPS measurements were performed on liver, palate, tongue, spleen and kidney 2, 4, 8, 24, 48, and 96 h after m-THPC administration. For validation of our FDPS measurements, liver and tongue were harvested for chemical extraction [2]. Concentration estimates in liver and tongue measured by FDPS are here compared with chemical extraction. At the HNODS-meeting we will present the results of our first step in the validation of FDPS; the correlation of FDPS measurements with chemical extraction for the three different formulations in the liver.

Oral Cavity : Early Lesions

The challenge in the treatment of early squamous cell carcinomas of the oral cavity and premalignant precursor lesions is to find a balance between efficacy and side effects. In early lesions, the tumor burden is low, and often treatment can be limited to local therapies. Development in the traditional therapies for early lesions is absent, in case of surgery and radiotherapy, and therefore other novel treatment strategies can provide the possibility of reducing side effects. Photodynamic therapy has proven to be effective and can be considered as an alternative to surgery or radiotherapy. Long-term side effects such as loss of sensitivity and tongue mobility seem lower after PDT. In this chapter, possible sensitizers are discussed that can be employed to treat early squamous cell carcinomas of the oral cavity.

In vivo quantification of mTHPC fluorescence in skinfold observation chamber using excitation and detection towards the near infrared region

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.