WST11, A Novel Water-soluble Bacteriochlorophyll Derivative; Cellular Uptake, Pharmacokinetics, Biodistribution and Vascular-targeted Photodynamic Activity Using Melanoma Tumors as a Model¶

Abstract

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 (t1/2=1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2=7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2=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/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.

Photodynamic therapy for Photogem® and Photofrin® using different light wavelengths in 375 human melanoma cells

“…This is understandable as melanin naturally acts protecting normal skin by screening white light [9,11,12,[24][25][26]. Poor responses then may be due to inappropriate levels of drug dose and light dose.…”

Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

“…Examples of clinical photosensitizers include hematoporphyrin derivatives (Photofrin)2 and aminolevulinic acid (ALA, a porphyrin precursor) 3. Two metal complexes are currently undergoing PDT clinical trials: TLD1433, an octahedral tris‐ N , N ‐chelated Ru II complex,4 and WST 11, a square‐planar Pd II bacteriochlorophyll derivative 5. Such complexes, together with octahedral Ir III complexes, are often luminescent and might be useful in theranostic procedures in which optical imaging is used to monitor the uptake of the sensitizer before subsequent irradiation then kills the cancer cells 6…”

Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

“…[3] Tw om etal complexes are currently undergoing PDT clinical trials: TLD1433, an octahedral tris-N,N-chelated Ru II complex, [4] and WST 11, as quare-planar Pd II bacteriochlorophyll derivative. [5] Such complexes,t ogether with octahedral Ir III complexes,a re often luminescent and might be useful in theranostic procedures in which optical imaging is used to monitor the uptake of the sensitizer before subsequent irradiation then kills the cancer cells. [6] Ak ey advantage for metal complexes is the heavy-atom effect, which favors fast singlet-to-triplet intersystem crossing (ISC), thus giving longer excited-state lifetimes [7] and higher yields of 1 O 2 and/or other so-called reactive oxygen species (ROS).…”