Stefan Spaniol

Photodynamic laser therapy with antibody-coupled phthalocyanine

We developed a new water-soluble phthalocyanine, activated for coupling to antibodies by N- hydroxysulfosuccinimide. The efficiency of anti-CA125-phthalocyanine conjugates was compared to free phthalocyanine in a human ovarian carcinoma model in tissue culture. In both cases a dose dependent cell killing was observed after irradiation with a Titanium sapphire laser at 675 nm and 50 J/cm2, but incubation with antibody-coupled phthalocyanine resulted in 90% cell mortality with a 60-130-fold lower dye application.

Optical fibers for improved light delivery in photodynamic therapy and diagnosis

For most Photodynamic Therapy (PDT) applications a diffuse, broad and uniform source of irradiation is needed to obtain the most effective and consistent treatment. Since many treatments are within the patients body, an effective compact fiber optic delivery system is needed for the activation of the photsensitizer drub at the site of the tissue to be treated. High Numerical Aperture (NA) optical fibers have benefits for PDT treatments but possibly even more so for PDT diagnostic applications These are summarized and new optical fibers with high and ultra high NAs are described. Properties of these fibers are presented as well as advantages they have over other fibers for delivering light in various PDT applications. Silica fibers with enhanced effective NAs approaching 0.6 are described.

Diffusing fiber tips for high-power medical laser applications

For most applications in laser medicine suitable delivery systems are required. We developed fiber optic based diffusing tips especially for photodynamic therapy (PDT) and laser induced thermotherapy (LITT). To realize an adequate emitting cylindrical diffuser the fiber core was abraded by a precision cutter. Hence, the use of scattering media such as TiO2-doped polymers is avoided. Because the diffuser size is mainly determined by the manipulated fiber and a surrounding glass capillary, one can realize small diameters ((phi) approximately equals 3 mm). The laser light is distributed mainly by surface scattering and total reflection at the fiber air boundary. Because the use of absorbing media is avoided, it is possible to apply high laser power as necessary in LITT and pulsed PDT. We produced diffusing tips with lengths of several centimeters and typical diameters of 3 mm. By controlling the fiber-shaping process, a homogeneous intensity profile or even special designs can be achieved. The control is done by either on-line camera surveillance or calculated predictions. A delivery system especially for the photodynamical treatment of female cervix dysplasia has been designed.

Comparison of Ti:sapphire laser and excimer-laser-pumped dye laser for PDT with Zn(II)-phthalocyanine

We compared the photodynamic efficiency of pulsed to cw laser irradiation in a cell culture experiment with a NIH ovarian cancer cell line (NIH-OVCAR3). Our photosensitizer was a cationic Zn(II)-phthalocyanine with an absorption maximum near 675 nm. The laser systems we use are an excimer laser pumped DCM-dye laser ((tau) equals 15 ns) and a cw Ti:sapphire laser. The photodynamic activity of the photosensitizer strongly depends on the pulse fluence and decreases with increasing fluence due to saturation of the sensitizer. In another experiment no changes in the light penetration depth into the tissue for pulsed irradiation could be detected up to a pulse intensity of 3 MW/cm2.

Palliative Therapie des Lokalrezidives bei Mammakarzinom durch PDT mit antikörpergebundenen Phthalocyaninen

Die Effektivitat der photodynamischen Therapie (PDT) mit antikorpergebundenem Zn-Phthalocyanin wurde im Zellkulturexperiment nachgewiesen. Eine Farbstoffkonzentration von 10 nM fuhrte bei Bestrahlung mit 50 J/cm2 zu 90% Zelltod.

Calculation of isofluence contours for PDT application

The aim of this study was to calculate the light fluence for various PDT applications with a Monte Carlo method. Different applicator geometries and the related illuminations are computed in a 3D-multilayer tissue model. The applicators we calculated include various surface geometries, intensity and angular profiles as well as tissue parameter variations, and different wavelengths. The resulting fluence contours in conjunction with a certain dye concentration allow a prediction of the expected damage zone after PDT in the tumor tissue. To measure tissue parameters ex vivo we built up a spectrometer consisting of two integrating spheres. The light source we use is a cw Ti:sapphire laser tunable from about 670 nm to 760 nm without change of optics. We use a combination of direct and indirect measurements. By estimating the specular reflection and direct transmission from a tissue sample (approximately 490 micrometers ) we get the refractive index n and the extinction coefficient (mu) (tau ). We also measure the diffuse reflection as well as the diffuse transmission with the integrating spheres. To calculate the missing parameters (mu) a and g we use an inverse Monte Carlo simulation (MCS) with the Henyey-Greenstein phase function. Simulation of the tissue sample including the boundary and geometry effects leads to absorption coefficients that are up to a factor of 3 lower in comparison to good analytical models. The loss of diffuse light can be taken into consideration.