Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

Abstract

Summary It has been proposed that the generation of 102 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on P02, in the murine RIF tumour during and after PDT using 5 mg kg-' Photofrin and fluence rates of 30, 75 or 150 mW cm-2. Median P02 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour P02 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm-2) P02 recovered at the 30 mW cm-2 fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm-2 fluence rate (median P02 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm-2 median tumour P02 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm-2 at 30 mW cm-2 caused significantly (P= 0.0004) longer median tumour regrowth times than PDT at 150 mW cm-2, indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour P02, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.

Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy

“…Although our pilot study showed no significant changes in oxygen saturation in either the ten patients monitored during standard MAL-PDT or the ten receiving the OPI intervention, the conclusion made from previous non-interventional oxygen monitoring studies (conducted with larger patient numbers), is that substantial changes in oxygenation can occur during and after PDT [31] and there is little debate surrounding the importance of oxygen during PDT. Oxygen can therefore be consumed in the photochemical reactions required for successful PDT more rapidly than it can be replenished [32].…”

Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study

“…12 However, in hypoxic conditions, it becomes less accurate for predicting the PDT efficacy since it does not consider the rate of PDT consumption of 3 O 2 for different ϕ. 15,16 With integration of the variation of 3 O 2 concentration (½ 3 O 2 ) into explicit dosimetry, a so-called singlet oxygen explicit dosimetry method based on mathematical modeling to calculate the 1 O 2 has made it possible to predict the PDT outcome. 17 For this purpose, an empirical four-parameter macroscopic 1 O 2 model was developed, and the reacted singlet oxygen (½ 1 O 2 rx ) was proposed as a dosimetry quantity for the accumulated concentration of 1 O 2 that is responsible for cellular killing and clinical outcomes.…”

Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for topically applied photosensitizers

“…(e) Power densities have been varied to study PDTinduced oxygen depletion [53,54], tissue response to PDT [37,55] or hyperthermia effects [56]. We have used two values (33 and 100 mW/cm 2 ) and have kept the light dose constant by varying the irradiation time.…”