Preclinical Comparison of mTHPC and Verteporfin for Intracavitary Photodynamic Therapy of Malignant Pleural Mesothelioma

Abstract

Efficacy and tumour selectivity of photodynamic therapy with two clinically approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM) at recommended drug-light conditions and at escalating sensitizer dosages. MPM tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell injection followed after 5 days by intracavitary PDT with light delivery monitored by in situ dosimetry. Animals were intravenously sensitized either with mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination with 20 J/cm² at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n = 3) followed after 20 min by illumination with 100 J/cm² at 689 nm. Three untreated tumour-bearing animals served as controls. Histological evaluation of the treated tumour and of adjacent normal organs was performed 10 days after tumour implantation. The extent of PDT-induced tumour necrosis was compared to the non-necrosed area and expressed in percentage. A locally invasive growing MPM tumour (3.1 ± 1 mm diameter) without spontaneous necrosis diameter was found in all animals. For both sensitizers, focal intracavitary PDT was well tolerated at drug-light conditions recommended for clinical applications. Mediastinal organs were spared for both sensitizers but verteporfin resulted in a higher extent of tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%, verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity than mTHPC-PDT.

Photodynamic therapy selectively enhances liposomal doxorubicin uptake in sarcoma tumors to rodent lungs

“…On the chick's chorioallantoic membrane model, Visudyne 1 -mediated PDT, at similar drug-light PDT conditions to those used in our study led to a temporary increase in effective permeability for macromolecules [13]. Visudyne 1 -mediated PDT also seemed appropriate for our setting as it had already been tested for the treatment of mesothelioma in rodents and was associated with insignificant lung injury at low drug-light conditions [25].…”

Temoporfin (Foscan®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer†,‡

“…A comparison of Foscan and Verteprofin intracavitary PDT on local malignant mesothelioma in the mediastinum of syngenic rats showed that both PS can be used. The PDT effect of verteporfin was better (264).…”

Photodynamic Therapy Enhances Liposomal Doxorubicin Distribution in Tumors during Isolated Perfusion of Rodent Lungs

“…We used verteporfin (Visudyne) for photosensitization because it is widely applied in the clinics for age-related macular degeneration [29]. Visudyne-mediated PDT of the chest cavity has been explored for the treatment of mesothelioma in rodents and was associated with no significant lung injury at low drug-light conditions [30]. The dynamic distribution of Visudyne is predominantly intravascular at 15 min after intravenous injection.…”