title: Correlation between in vivo pharmacokinetics, intratumoral distribution and photodynamic efficiency of liposomal mTHPC.
abstract: Foslip is a recently designed third generation photosensitiser based on unilamellar dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) liposomal formulations of meta-tetra(hydroxyphenyl)chlorine (mTHPC). The present study investigates Foslip behaviour and its photodynamic efficiency in EMT6 xenografted nude mice at different times following i.v. administration of 0.3 mg kg(-1) mTHPC in a Foslip formulation. Plasma pharmacokinetics and biodistribution were studied by high performance liquid chromatography and were described by a three compartments analysis with half-lifes of 0.13, 4.31 and 35.7 h. The highest tumour to muscle ratios were observed at 6 and 15 h post-administration. Intratumoral distribution was carried out using two photon excitation confocal microscopy. Progressive efflux from the vascular compartment was noted in favour of tumour parenchyma, which was almost completed at 15 h. The best tumour response was obtained for a drug-light interval of 6 h, interval for which mTHPC was present in both endothelial and parenchyma cells. Tumour and plasma concentrations however were far below their maximal values. Based on these observations, we assume that the presence of mTHPC in both vasculature and tumour cells is required for optimal PDT efficacy.
authors.affiliation: Centre de Recherche en Automatique de Nancy, Nancy Université, CNRS, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France. h.lassalle@nancy.fnclcc.fr
authors.forename: Henri-Pierre
authors.initials: HP
authors.lastname: Lassalle
authors.forename: Dominique
authors.initials: D
authors.lastname: Dumas
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: D'Hallewin
authors.forename: François
authors.initials: F
authors.lastname: Guillemin
authors.forename: Lina
authors.initials: L
authors.lastname: Bezdetnaya
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage; D000818:Animals; D005260:Female; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010715:Phosphatidylglycerols / Q000008:administration & dosage; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D008081:Liposomes; D008652:Mesoporphyrins; D010715:Phosphatidylglycerols; D017319:Photosensitizing Agents; D015060:1,2-Dipalmitoylphosphatidylcholine; C072269:temoporfin; C030345:1,2-dipalmitoylphosphatidylglycerol