PDT photo activation irradiance monitoring during a Phase I clinical study of TLD1433 in bladder cancer (Conference Presentation)

While Photofrin mediated PDT for bladder cancer was the first approved indication for this technique, it failed to attract the confidence of urologists as a treatment option, primarily due to the high incidence of incontinence linked to PDT damage to the bladder muscle. To mitigate this hazard a phase I clinical trial using instillation of the Ru(II) coordination complex TLD1433 and 530 nm activation light was initiated. To achieve the intended drug doses of 0.35 and 0.7 mg/cm2 and a radiant exposure of 90 J/cm2 the concentration of the instillation was adjusted to each patients' bladder volume and the irradiance was measured at up to 12 positions in the bladder. Irradiance monitoring proved helpful in adjusting the irradiation time to the bladder wall albedo and also for increased light scattering and absorption due to turbidity built up in the bladder void. The initial multiplication factors of the bladders (n=6) ranged from 1.1 to 2.8. Monte Carlo simulations based on CT-scans from all 6 participants approximate the range of irradiances observed during these studies. Nevertheless, a fraction of the surface can see a multiple of the average irradiance whereas other regions (typically less than 5% of the surface area) see significantly less than the average irradiance. These variations are due to the actual bladder shape and are somewhat independent of the position of the spherical emitter. Fitting of the measured surface irradiance to the simulated dose surface histograms enables extraction of the bladder wall and bladder void’s optical properties.