Premium
Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels tumor vascular density
Author(s) -
Wang Yabo,
Gonzalez Michel,
Cheng Cai,
Haouala Amina,
Krueger Thorsten,
Peters Solange,
Decosterd LaurentArthur,
van den Bergh Hubert,
Perentes Jean Y.,
Ris HansBeat,
Letovanec Igor,
Debefve Elodie
Publication year - 2012
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22013
Subject(s) - sarcoma , medicine , adenocarcinoma , mesothelioma , pathology , doxorubicin , lung , photodynamic therapy , cancer , chemotherapy , chemistry , organic chemistry
Background Visudyne®‐mediated photodynamic therapy (PDT) at low drug/light conditions has shown to selectively enhance the uptake of liposomal doxorubicin in subpleural localized sarcoma tumors grown on rodent lungs without causing morphological alterations of the lung. The present experiments explore the impact of low‐dose PDT on liposomal doxorubicin (Liporubicin™) uptake to different tumor types grown on rodent lungs. Material and Methods Three groups of Fischer rats underwent subpleural generation of sarcoma, mesothelioma, or adenocarcinoma tumors on the left lung. At least five animals of each group (sarcoma, n = 5; mesothelioma, n = 7; adenocarcinoma, n = 5) underwent intraoperative low‐dose (10 J/cm 2 at 35 mW/cm 2 ) PDT with 0.0625 mg/kg Visudyne® of the tumor and the lower lobe. This was followed by intravenous (IV) administration of 400 µg Liporubicin™. After a circulation time of 60 min, the tumor‐bearing lung was processed for HPLC analyses. At least five animals per group underwent the same procedure but without PDT (sarcoma, n = 5; mesothelioma, n = 5; adenocarcinoma, n = 6). Five untreated animals per group underwent CD31 immunostaining of their tumors with histomorphometrical assessment of the tumor vascularization. Results Low‐dose PDT significantly enhanced Liporubicin™ uptake to all tumor types (sarcoma, P = 0.0007; mesothelioma, P = 0.001; adenocarcinoma, P = 0.02) but not to normal lung tissue compared to IV drug administration alone. PDT led to a significantly increased ratio of tumor to lung tissue drug uptake for all three tumor types ( P < 0.05). However, the tumor drug uptake varied between tumor types and paralleled tumor vascular density. The vascular density was significantly higher in sarcoma than in adenocarcinoma ( P < 0.001) and mesothelioma ( P < 0.001), whereas there was no significant difference between adenocarcinoma and mesothelioma. Conclusion Low‐dose Visudyne®‐mediated PDT selectively enhances the uptake of systemically administered liposomal doxorubicin in tumors without affecting the drug uptake to normal lung. However, drug uptake varied significantly between tumor types and paralleled tumor vascular density. Lasers Surg. Med. 44:318–324, 2012. © 2012 Wiley Periodicals, Inc.