Interstitial Doppler optical coherence tomography monitors microvascular changes during photodynamic therapy in a Dunning prostate model under varying treatment conditions

Abstract

We measure the tumor vascular response to varying irradiance rates during photodynamic therapy (PDT) in a Dunning rat prostate model with interstitial Doppler optical coherence tomography (IS-DOCT). Rats are given a photosensitizer drug, Photofrin, and the tumors are exposed to light (635 nm) with irradiance rates ranging from 8 to 133 mWcm(2) for 25 min, corresponding to total irradiance of 12 to 200 Jcm(2) (measured at surface). The vascular index computed from IS-DOCT results shows the irradiance rate and total irradiance dependent microvascular shutdown in the tumor tissue during PDT. While faster rates of vascular shutdown were associated with increasing PDT irradiance rate and total irradiance, a threshold effect was observed as irradiance rates above 66 mWcm(2) (surface), where no further increase in vascular shutdown rate was detected. The maximum post-treatment vascular shutdown (81%) without immediate microcirculatory recovery was reached with the PDT condition of 33 mWcm(2) and 50 Jcm(2). Control groups without Photofrin show no significant microvascular changes. Microvascular shutdown occurs at different rates and shows correlation with PDT total irradiance and irradiance rates. These dependencies may play an important role in PDT treatment planning, feedback control for treatment optimization, and post-treatment assessment.