Evaluation of the Photosensitizer Tookad® for Photodynamic Therapy on the Syrian Golden Hamster Cheek Pouch Model: Light Dose, Drug Dose and Drug–light Interval Effects¶

Abstract

We have evaluated the efficacy of the new photosensitizer (PS) Tookad in photodynamic therapy (PDT) in vivo. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 762 and 538 nm. The light dose, drug dose and drug injection-light irradiation interval (DLI), ranging between 100 and 300 J/cm2, 1 and 5 mg/kg and from 10 to 240 min, respectively, were varied, and the response to PDT was analyzed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. The level of PDT response, macroscopically and histologically, shows a strong dependence on the DLI, light dose and drug dose at the applied conditions in the normal hamster cheek pouch. A decay of the tissular response with increasing DLI is observed corresponding to a time of half-maximum response ranging from 10 to 120 min, depending on drug dose and light dose. The tissues affected at the lowest doses are predominantly the vascularized diffuse connective tissue situated between the inner and outer striated muscle (SM) layers as well as these muscle layers themselves. The highest response at the shortest DLI and the absence of a measurable response at DLI longer than 240 min at 300 J/cm2 and drug dose of 5 mg/kg are characteristics of a predominantly vascular effect of this PS. This observation suggests that Tookad could be effective in PDT of vascularized lesions or pathologies associated with the proliferation of neovessels.

Photodynamic therapy with WST09 (Tookad): Quantitative studies in normal colon and transplanted tumours

“…The initial effects with WST09 are predominantly vascular, whereas with the longer acting agents they usually involve both vascular and cellular damage, but by the time the full extent of the lesion has become apparent, there are no obvious differences. We did not see damage limited to the submucosal region, as described by Borle et al 11. in the hamster cheek pouch, perhaps because the glandular mucosa of the colon is more vulnerable to vascular damage in the submucosa than the squamous mucosa of the cheek.…”

“…It is unlikely that it will be possible to achieve truly selective tumour necrosis when tumour and adjacent normal tissue in which the tumour arose are exposed to the same light dose, although we did get close to this with some of the colon tumours. Borle et al 5, 11. have demonstrated a more severe effect in squamous carcinomas of the hamster cheek pouch than in contra‐lateral normal tissue in the same animals, although the threshold doses for producing any effect were the same in both areas.…”

Magnetic resonance imaging correlated with the histopathological effect of Pd‐bacteriopheophorbide (Tookad) photodynamic therapy on the normal canine prostate gland

“…Tookad-PDT produces cytotoxic reactive oxygen species which lead to vascular occlusion, stasis, and resultant necrosis [31,32]. MRI offers a variety of methods for assessing these treatment responses.…”

Unique Diagnostic and Therapeutic Roles of Porphyrins and Phthalocyanines in Photodynamic Therapy, Imaging and Theranostics

“…The two modalities (fluorescence imaging and pdt) work on the same basic principles - illumination and photochemistry but differ greatly in their desired outcome - fluorescence imaging has minimal/no cytotoxicity due to the low fluence rate used to generate light activation, whereas in pdt, where a cytotoxic effect is the goal of the treatment, a high fluence rate is used to generate the singlet oxygen necessary to elicit cell death 194. Both the uniqueness and major advantage of using fluorescence imaging and pdt in combination with each other is that the same entity can act as both the imaging and therapeutic agent, the only known exception to this is TOOKAD ® , the palladium-complexed bacteriochlorophyll (figure 20); TOOKAD ® has a negligible fluorescence quantum yield 229, 230. This emphasises the potential of fluorescence imaging in pdt for the diagnosis, guided therapy and monitoring of surgery (or in other therapies) - the therapeutic outcome in the treatment of disease can be made more robust by utilising all of the available forms of imaging and guidance techniques/technologies.…”