aluminum-phthalocyanine-disulfonate and Prostatic-Neoplasms

Further to our work on the feasibility of application of photodynamic therapy (PDT) to the canine prostate, this study evaluates the biological responses of the prostate and adjacent vital structures with meso-tetra-(m-hydroxylphenyl) chlorin (mTHPC) or aluminum disulfonated phthalocyanine (AlS2Pc) based PDT as a preparatory step for clinical trials. Skin photosensitivity was not particularly problematic if light protection could be implemented properly for 2 weeks following sensitization. Prostate PDT was well tolerated by the experimental animals with only minor physical distress. mTHPC was more powerful than AlS2Pc in terms of prostate lesions induced. A large portion of prostate tissue could be destroyed by PDT with 4 punctures. Physical distress was probably caused by severe urethral irritation and aching from acute swelling of the prostate. Although the voiding condition normalized within 10 days, regeneration of urethral epithelium was not complete until 3-4 weeks after PDT. Improper placement of laser fiber caused extensive ecchymosis of the retroperitoneal organs. The biological significance of PDT induced hyperemia in the periprostatic structures remains poorly defined. Neither periprostatic nerve damage nor rectal lesions were seen in dogs receiving either mTHPC or AlS2Pc. Glandular atrophy with papillary cystic regeneration of the prostate was the most prominent finding 90 days after PDT. The glandular architecture was well preserved because the interlobular collagens were less affected than the cellular components of the glands. Our study suggests that PDT with mTHPC and AlS2Pc is safe and promising for necrosing a substantial amount of prostate tissue. The completeness of treatment and long-term therapeutic effectiveness for prostate cancer, however, remains to be determined through further investigation.

Topics: Animals; Dogs; Epithelium; Indoles; Male; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Rectal Diseases; Skin; Urethral Diseases; Urination Disorders

Photodynamic therapy (PDT) is an experimental approach for treating prostate cancer localized to the gland that does not involve surgery or irradiation. Second-generation photosensitizers 5-aminolevulinic acid (ALA) and aluminum disulfonated phthalocyanine (AlS2Pc) were studied in the normal canine prostate.. Tissue biodistribution of photosensitizers on serial biopsies was examined using fluorescence microscopy. Photodynamic therapy was done by delivering red light interstitially at 100 mW through fibers placed under transrectal ultrasound guidance.. Peak levels of AlS2Pc appeared at 5-24 hr and at 3 hr for ALA. Macroscopic PDT lesions were up to 12 mm in diameter using AlS2Pc, but only 1-2 mm with ALA. Light at 300 mW caused thermal lesions. At 28 days, damaged glands remained atrophic, but the interlobular supporting stroma was well-preserved. Urethral lesions healed by 28 days without functional impairment.. Although the results with ALA were disappointing, PDT using AlS2Pc looks like a promising modality for treatment of localized prostate cancer.

Topics: Aminolevulinic Acid; Animals; Atrophy; Collagen; Dogs; Indoles; Lasers; Light; Male; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Prostate; Prostatic Neoplasms; Protoporphyrins