Journal
PHOTOCHEMISTRY AND PHOTOBIOLOGY
Volume 81, Issue 2, Pages 342-351Publisher
WILEY
DOI: 10.1562/2004-06-14-RA-199.1
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WST11 is a novel negatively charged water-soluble palladium-bacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t(1/2) = 1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t(1/2) = 7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t(1/2) = 20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm(2). These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.
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