At present, the intended goal of PDT dosimetry is to curtail or modify the optical energy delivery throughout the clinical target volume following a predetermined photosensitizer administration and empirically determined light source spacing under consideration of the anatomical limitations. The underlying assumption is that the photosensitizer’s specific uptake ratio in the target over the surrounding normal tissues is large enough to compensate for intra and interpatient variability in the dose due to differences in the photosensitizer accumulation and local pO2.
Treatment failure is often attributed to insufficient local or global photosensitizer and/or oxygen concentration in the clinical target volume.
Monitoring the photosensitizer fluorescence during interstitial PDT may undersample the spatial distribution of the photosensitizer concentration, and the current empirical placement of interstitial light sources can not mitigate this spatial dose variability, particularly at the edge of the target volume.
Knowledge of the spatial photosensitizer and oxygen availability is desirable for providing patient-centred PDT light treatment planning. However, what spatial resolution is required to derive different treatment plans? How can the spatial oxygen and photosensitizer distribution be predicted prior to the placement of the light emitters?
Ongoing in silico studies aim to determine the impact of varying spatial resolution in the photosensitizer and oxygen concentration quantification on PDT treatment planning solutions. The variability of the photosensitizer concentration is modelled based on in vivo fluorescence imaging studies of intracranial and subcutaneous tumour models. Comparison with fMRI studies imaging blood flow and blood volume indicate that the mean transit time of blood is a good indicator for the local photosensitizer accumulation.
Hence, the spatial quantification of blood flow and volume as biomarkers for photosensitizer and oxygen availability can be used to for the local PDT dose description, leading to improved tumour eradication.
What are the remaining uncertainties? Independent of how many PDT efficacy-determining parameters the ‘dose’ definition is based on, the influence of other stressors and the biological microenvironment on the minimum dose to cause cell death remains poorly studied.