Back to Basics and facts ! CONCLUSIONS
Combination of TLD1433 instillation and the use of green PDT activation light results in a steep PDT gradient providing one avenue to protect normal muscle function. The high selective uptake of TLD1433 is very favorable to compensate for heterogeneities in the bladder wall irradiance, and the absence of visible damage to the muscle layers also opens an avenue for the treatment of MIBC in addition to targeting NMIBC. Based on the threshold calculation, the selectivity of TLD1433 mediated PDT can be maintained over two penetration depths, possibly significantly more if the true tumor and urothelium threshold values can be determined for human cases. This is also very favorable as for human cases of MIBC, longer wavelength per target tissue penetration depth could be employed, mainly because of the apparent low TLD1433 concentrations in the muscle layers and the ability to activate the photosensitizer across a broad optical spectrum.
This study does not address possible caveats for the clinical translation of TLD1433 mediated PDT for NMIBC. For example, the urothelial layer over the tumor must be compromised for the photosensitizer to gain access to the malignant cells. Therefore, a tumor growing under an intact urothelial layer may not be sensitized by instillation alone. Also, NMIBC can be present upstream of the bladder, which is not targeted by PDT limited to intravesical illumination and bladder cancer cells as cancer cells may shed upstream and reseed on the bladder wall denuded of the urothelium, suggesting that for clinical use, repeat treatments may be advisable.
The excellent safety aspects, based on the large SUR, and the steep PDT gradient due to the use of short, green activation wavelength, makes TLD1433 mediated PDT an excellent candidate for NMIBC.
Evaluation of a Ruthenium coordination complex as photosensitizer for PDT of bladder cancer: Cellular response, tissue selectivity and in vivo response - Lilge - 2020 - Translational Biophotonics - Wiley Online Library