The biology of photodynamic therapy in the bladder and prostate

Photodynamic therapy (PDT) produces localised destruction of tissue with light after prior administration of a photosensitising agent. Connective tissue is relatively unaffected but attempts to treat the entire urothelium in the bladder using the photosensitiser Photofrin have led to detrusor muscle scarring and irritable, contracted bladders and obstructive uropathy. This thesis studied PDT on the normal rat bladder using the photosensitising agent, 5-aminolaevulinic acid (ALA). ALA solution was given intravesically, and the kinetics of the active derivative, protoporphyrin IX (PpIX) followed with fluorescence microscopy. Peak urothelial levels were seen at 5 hours, when treatment with 50J red light gave uniform urothelial necrosis without muscle damage which healed by regeneration. The PDT effect was enhanced by giving the iron chelator, CP94. Further studies looked at PDT on normal canine prostate using 3 photosensitisers: ALA, meso-tetra-(m-hydroxyphenyl)chlorin (mTHPC) and aluminium disulphonated phthalocyanine (A1S2Pc). Kinetic studies were undertaken on serial biopsies after sensitisation. Light was delivered interstitially and the animals killed up to 90 days later, revealing glandular necrosis (2.5cm diam. mTHPC, 1.2cm A1S2PC, 0.2cm ALA) but little effect on connective tissues, and no change in the gland size and shape. Urethral damage sometimes caused urinary retention which resolved in a week. Deliberate treatment of the sphincter in rats caused incontinence in 25%. Neoplastic areas of both prostate and bladder take up at least as much photosensitiser as adjacent normal tissue. Thus PDT using intravesical ALA is promising for carcinoma in situ of the bladder and preventing bladder tumour recurrence and PDT with mTHPC for prostate cancers localised to the gland, care being taken to avoid the sphincter. Both techniques are now ready for preliminary clinical trials.