Evaluation of a Ruthenium coordination complex as photosensitizer for PDT of bladder cancer: Cellular response, tissue selectivity and in vivo response. Issue 1 (11th March 2020)

• Record Type: Journal Article
• Authors: Lilge, Lothar; Roufaiel, Mark; Lazic, Savo; Kaspler, Pavel; Munegowda, Manjunatha A.; Nitz, Mark; Bassan, Jay; Mandel, Arkady
• Other Names: Philipp Carsten guestEditor.; Sroka Ronald guestEditor.
• Is Part Of: Translational biophotonics. Volume 2:Issue 1/2(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-11
• Subjects: Imaging systems in medicine -- Periodicals; Biosensors -- Optical properties -- Periodicals; Photonics -- Periodicals; Imaging systems in medicine; Photonics; Optics and Photonics; Translational Medical Research; Periodicals; Periodical; 621.365
• DOI: 10.1002/tbio.201900032
• Languages: English
• ISSNs: 2627-1850

Abstract

Abstract: TLD1433, a Ru(II) polypyridyl complex, was recently introduced. It can be activated in the 520 to 540 nm range. Here we report on the use of TLD1433 for the treatment of bladder carcinomas in vitro and in an in vivo orthotopic model. The electrostatic properties of the normal urothelium vs a tumor compromised urothelium provide for a high selective uptake ratio. In vitro, a 1000 difference in the LD50 between dark and 22.5 J cm −2 irradiation at 530 nm was achieved for two bladder cell lines (T24 and AY‐27). In dogs and rats the plasma concentration for TLD1433 was below 100 ng kg −1 at 72 hours following intravenous injection at a dose of up to 3.5 mg kg −1 and below 10 ng kg −1 following intrabladder instillation for 1 hour at a concentration of 6 mg mL −1 . Successful tumor necrosis close to 1.5 mm in depth was achieved. Abstract : The efficacy of green light mediated PDT post photonsensitizer instillation was evaluated in an orthotopic bladder cancer model. The photosensitizer is a novel Ruthenium Coordination complex. The study demonstrated a very high selective uptake into the model tumour system and complete tumour eradication to a depth of >1 mm without damage to the bladder muscle. The PDT selectivity seen here is very promising for future translation into the clinic.