Spatial distribution of liposome encapsulated tin etiopurpurin dichloride (SnET2) in the canine prostate: implications for computer simulation of photodynamic therapy.

Photodynamic therapy (PDT) is a minimally invasive treatment that can be employed in many human diseases including prostate cancer. PDT for prostate cancer depends on the sequestration of a photosensitizing drug within the glandular tissue. The photosensitizer is subsequently activated by light (usually from a laser) and the active drug destroys tissue. Since prostate cancer is a multifocal disease, PDT must ablate the glandular prostate completely. This will depend on the precise placement of light sources in the prostate and delivery of a therapeutic light dose to the entire gland. Also, sources of light and their spatial distribution must be tailored to each individual patient. The uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. To help achieve the uniform light distribution throughout the prostate we have developed a computer program that can determine treatment effects. The program predicts the best set of parameters and the position of light diffusers in space, and displays them in graphical or in numerical form assuming a fixed attenuation coefficient. The two parameters of greatest importance in the computer simulation are attenuation coefficient and critical fluence. Both depend on the concentration of active drug within the prostate gland. It is necessary to know the nature of the spatial distribution of photosensitizer within the prostate to execute computer modeling of PDT with high precision. We found that the concentration of SnET2 is heterogeneous in nature, and is higher in the proximity of the glandular capsule. It is clear therefore that any future attempts of computerized modeling of this procedure must take into consideration the uneven sequestration of photosensitizer and the consequential asymmetrical necrosis of the prostate.

[1]  C J Gomer,et al.  Photodynamic therapy in the treatment of malignancies. , 1989, Seminars in hematology.

[2]  D. Kessel,et al.  PHOTOSENSITIZATION WITH DERIVATIVES OF CHLOROPHYLL , 1989, Photochemistry and photobiology.

[3]  B. Overholt,et al.  Comparative pharmacokinetics of the photosensitizer tin-etiopurpurin in dogs and rats. , 1992, Journal of veterinary pharmacology and therapeutics.

[4]  T. Chang,et al.  Purification and characterization of liposomes encapsulating hemoglobin as potential blood substitutes. , 1992, Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology.

[5]  S Kölchens,et al.  Quasi-elastic light scattering determination of the size distribution of extruded vesicles. , 1993, Chemistry and physics of lipids.

[6]  D. Kessel,et al.  THE ROLE OF LIPOPROTEINS IN THE DISTRIBUTION OF TIN ETIOPURPURIN (SnET2) IN THE TUMOR‐BEARING RAT , 1993, Photochemistry and photobiology.

[7]  R W Keck,et al.  The effect of transurethral light on the canine prostate after sensitization with the photosensitizer tin (II) etiopurpurin dichloride: a pilot study. , 1994, The Journal of urology.

[8]  C. Gomer,et al.  Clinical and preclinical photodynamic therapy , 1995, Lasers in surgery and medicine.

[9]  C. Gomer,et al.  Photosensitization with derivatives of chlorin p6. , 1995, Journal of Photochemistry and Photobiology. B: Biology.

[10]  S L Marcus,et al.  Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status , 1996, Photonics West.

[11]  L. O. Svaasand,et al.  A mathematical model for light dosimetry in photodynamic destruction of human endometrium. , 1996, Physics in medicine and biology.

[12]  Stuart L. Marcus,et al.  Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status. , 1996 .

[13]  R. Keck,et al.  Transperineal photodynamic ablation of the canine prostate. , 1996, The Journal of urology.

[14]  Shi-Chung Chang,et al.  Interstitial and transurethral photodynamic therapy of the canine prostate using meso‐tetra‐(m‐hydroxyphenyl) chlorin , 1996, International journal of cancer.

[15]  B. Wilson,et al.  Changes in in vivo optical properties and light distributions in normal canine prostate during photodynamic therapy. , 1997, Radiation research.

[16]  S. Jacques,et al.  Light Distributions from Point, Line and Plane Sources for Photochemical Reactions and Fluorescence in Turbid Biological Tissues , 1998, Photochemistry and photobiology.

[17]  F Martelli,et al.  Study on the propagation of ultra-short pulse light in cylindrical optical phantoms. , 1999, Physics in medicine and biology.

[18]  Steven H. Selman,et al.  Computer model for photodynamic therapy of the prostate , 2000, Photonics West - Biomedical Optics.

[19]  C. Kim,et al.  Prolonged Blood Circulation of Methotrexate by Modulation of Liposomal Composition , 2001, Drug delivery.

[20]  S. Moghimi,et al.  Modulation of murine liver macrophage clearance of liposomes by diethylstilbestrol. The effect of vesicle surface charge and a role for the complement receptor Mac-1 (CD11b/CD18) of newly recruited macrophages in liposome recognition. , 2002, Journal of controlled release : official journal of the Controlled Release Society.