Chlorin e6 - polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts.
BACKGROUND
Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung cancers. The present study evaluated the potential use of chlorin e6 - polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC xenografts.


RESULTS
Human NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines were used to establish tumor xenografts in the chick chorioallantoic membrane (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was applied topically (1.0 mg/kg) and fluorescence intensity was charted at various time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6-PVP has a selective localization and a good accuracy in demarcating NSCLC compared to SCLC from normal surrounding CAM after 3 h post drug administration. Irradiation at 3 h drug-light interval showed greater tumor necrosis against human NSCLC xenografts in nude mice. SCLC xenografts were observed to express resistance to photosensitization with Ce6-PVP.


CONCLUSIONS
The formulation of Ce6-PVP is distinctly advantageous as a diagnostic and therapeutic agent for fluorescence diagnosis and PDT of NSCLC.
Division of Medical Sciences, 11 Hospital Drive, Singapore 169610, National Cancer Centre, Singapore. chin.will@gmail.com
William W L
WW
Chin
Paul W S
PW
Heng
Malini
M
Olivo
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002735:Chlorophyllides; D049033:Chorioallantoic Membrane / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011205:Povidone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin; D011205:Povidone