Interstitial and transurethral photodynamic therapy of the canine prostate using meso-tetra-(m-hydroxyphenyl) chlorin

Abstract

Photodynamic therapy (PDT) produces localised necrosis with light after prior administration of a photosensitising drug. Although the technique is promising for small tumours of hollow organs, little work has been done on solid organs like the prostate. We studied the tissue biodistribution and photodynamic effects of meso-tetra-(m-hydroxyphenyl) chlorin (mTHPC), a potent second-generation photosensitiser, on normal canine prostate in vivo. Using quantitative fluorescence microscopy, the highest concentration of mTHPC in the prostate was seen 24-72 hr after intravenous administration. For PDT, red light (650 nm) was delivered to the prostate by laser fibres inserted via the transurethral or transperineal route under transrectal ultrasound guidance. PDT lesions up to 40 mm in diameter (using 4 fibre sites) were produced, characterised by swelling, inflammatory response and extensive glandular destruction. There was persistent glandular atrophy at 90 days, but no disruption of the main stroma and no change in the ultimate size or shape of the gland. Urethral damage sometimes caused temporary urinary retention, but this resolved by 7 days, and no animal became incontinent. Occasional small lesions were seen in the rectum, but these healed without sequelae and there were no fistulae. Since cancer and normal prostate are likely to respond similarly, PDT has considerable promise for treating cancer confined to the gland as large areas of glandular tissue can be necrosed with safe healing. Because the structural integrity of the gland is maintained, PDT is unlikely to be of value in the management of benign prostatic hypertrophy.