Preclinical Studies in Normal Canine Prostate of a Novel Palladium-Bacteriopheophorbide (WST09) Photosensitizer for Photodynamic Therapy of Prostate Cancer¶

Abstract

Photodynamic therapy (PDT) uses light to activate a photosensitizer to achieve localized tumor control. In this study, PDT mediated by a second‐generation photosensitizer, palladium‐bacteriopheophorbide WST09 (Tookad) was investigated as an alternative therapy for prostate cancer. Normal canine prostate was used as the animal model. PDT was performed by irradiating the surgically exposed prostate superficially or interstitially at 763 nm to different total fluences (100 or 200 J/cm2; 50, 100 or 200 J/cm) at 5 or 15 min after intravenous administration of the drug (2 mg/kg). Areas on the bladder and colon were also irradiated. The local light fluence rate and temperature were monitored by interstitial probes in the prostate. All animals recovered well, without urethral complications. During the 1 week to 3 month posttreatment period, the prostates were harvested for histopathological examination. The PDT‐induced lesions showed uniform hemorrhagic necrosis and atrophy, were well delineated from the adjacent normal tissue and increased linearly in diameter with the logarithm of the delivered light fluence. A maximum PDT‐induced lesion size of over 3 cm diameter could be achieved with a single interstitial treatment. There was no damage to the bladder or rectum caused by scattered light from the prostate. The bladder and rectum were also directly irradiated with PDT. At 80 J/cm2, a full‐depth necrosis was observed but resulted in no perforation. At 40 J/cm2, PDT produced minimal damage to the bladder or rectum. On the basis of optical dosimetry, we have estimated that 20 J/cm2 is the fluence required to produce prostatic necrosis. Thus, the normal structure adjacent to the prostate can be safely preserved with careful dosimetry. At therapeutic PDT levels, there was no structural or functional urethral damage even when the urethra was within the treated region. Hence, Tookad‐PDT appears to be a promising candidate for prostate ablation in patients with recurrent, or possibly even primary, prostate cancer.

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

“…Tookad is the second generation sensitizer with the longest wavelength absorption peak at 763 nm, and it is under consideration for treatment of larger lung tumors and associated lung obstructions in human patients. Tookad PDT has been documented to lead to tumor necrosis at a depth of 1.3 cm for WISH-PC2 mouse xenografts (39) and to induce 3 cm diameter lesions in the canine prostate (40). The maximal depth efficacy of our new sensitizers is expected to be considerably more than that that indicated above.…”

Photodynamic therapy in the treatment of prostate cancer

“…Najmniejsza dawka powodująca martwicę tkanek stercza wynosiła 20 J/cm 2 . Bezpośrednie naświetlanie tkanek przyległych dawką 40 J/cm 2 powodowało ich uszkodzenie, a dawką 80 J/cm 2 -martwicę, jednakże podczas naświetlania stercza nie obserwowano uszkodzenia tych tkanek, nawet przy stosowaniu dawek wielokrotnie większych (100-200 J/cm 2 ) [47]. Podobnie Huang i wsp., stosując WST-09 wobec zdrowych psów, nie stwierdzili po naświetlaniu uszkodzenia przyległych tkanek.…”

Treatment planning using tailored and standard cylindrical light diffusers for photodynamic therapy of the prostate

“…Reports coincide to find sizable variations of the optical properties within the prostate and among different subjects (see for example (Muschter 2003), (Martin and Hahn 2004) and references therein). Furthermore, light delivery has been shown to affect the optical properties at some wavelengths (630 nm (Chen et al 1997) and 670 nm (Ballangrud et al 1997)), but not at longer ones (732 nm (Zhu et al 2003) and 763 nm (Chen et al 2002)). These data suggest that oxygen consumption plays a big role in this phenomenon since haemoglobin displays strong absorption in the 600 to 700 nm region.…”

“…Some photosensitizers such as ALA (Zaak et al 2003) and Motexium Lutetium (Hsi et al 2001) do not show a clear relationship between depth of necrosis and light dose. Others such as SnET 2 (Selman et al 2001) and WST09 (Chen et al 2002) do support a threshold model. This study is divided in two parts.…”