Quantitative analysis of lesion images to evaluate the efficiency of vascular-targeted photodynamic therapy for port-wine stains: Four case reports.

SIGNIFICANCE: Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For accurate treatment, varying light irradiance is required for different lesions due to the irregularity of vascular size, shape and degree of disease, which commonly alters during different stages of V-PDT. This makes quantitative analysis of the treatment efficiency urgently needed. APPROACH: Lesion images pre- and post- V-PDT treatment of patients with PWS were used to construct a quantitative method to evaluate the differences among lesions. Image analysis techniques were applied to evaluate the V-PDT efficiency for PWS by determining the Euclidean distances and two-dimensional correlation coefficients. RESULTS: According to the image analysis, V-PDT with good treatment efficiency resulted in a larger Euclidean distance and a smaller correlation coefficient compared with the case having lower V-PDT efficiency. CONCLUSIONS: A new method to quantify the Euclidean distances and correlation coefficients has been proposed, which is promising for the quantitative analysis of V-PDT efficiency for PWS.

Synthesis, Photo-Characterizations, and Pre-Clinical Studies on Advanced Cellular and Animal Models of Zinc(II) and Platinum(II) Sulfonyl-Substituted Phthalocyanines for Enhanced Vascular-Targeted Photodynamic Therapy.

Two phthalocyanine derivatives tetra-peripherally substituted with tert-butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO2tBu demonstrated an outstanding ability to generate singlet oxygen (ΦΔ = 0.87-0.99), while ZnSO2tBu in addition to 1O2 (ΦΔ = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log Pow) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of ZnSO2tBu and 100% of PtSO2tBu-treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO2tBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.

Monitoring perfusion and oxygen saturation in port-wine stains during vascular targeted photodynamic therapy.

BACKGROUND: Vascular targeted photodynamic therapy (V-PDT) is a safe and effective therapeutic modality for port-wine stains (PWS) by targetedly damaging the dilated and malformed blood vessels. This study aims to monitor and quantify the changes in oxygen saturation (StO2), blood volume fraction (BVF) and perfusion in PWS lesions before and during V-PDT. METHODS: Microvascular parameters (i.e., StO2 and BVF) and skin perfusion were measured noninvasively by using diffuse reflectance spectroscopy (DRS) and laser Doppler imaging (LDI), respectively. The change in StO2, BVF and perfusion that occurred in the PWS lesions of 26 patients were monitored and investigated before and during V-PDT in vivo with the systematic administration of the porphyrin-based photosensitizer HiPorfin. RESULTS: The mean StO2 (P<0.05), BVF (P<0.05), and perfusion (P<0.001) in PWS lesions of all subjects significantly increased by 6%, 34%, and 113%, respectively, 3 min after the initiation of V-PDT. The StO2 increased first and fluctuated during V-PDT. The overall trend of BVF change was consistent with the perfusion change. The BVF and the perfusion of PWS lesions increased after the initiation of V-PDT, and then gradually decreased. CONCLUSIONS: V-PDT is an effective therapeutic modality in treating PWS. Results showed that LDI and DRS permitted the noninvasive monitoring of the changes in StO2, BVF, and perfusion in PWS lesions during V-PDT, and these methods can be useful in facilitating our understanding of the basic physiological mechanisms during V-PDT.