BIODISTRIBUTION AND PDT EFFICACY OF A KETOCHLORIN PHOTOSENSITIZER AS A FUNCTION OF THE DELIVERY VEHICLE

Abstract C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a l ipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.     

IMPAIRED ACCUMULATION OF A CATIONIC PHOTOSENSITIZING AGENT BY A CELL LINE EXHIBITING MULTIDRUG RESISTANCE

Abstract —Transport and accumulation of copper benzochlorin iminium salt (CDSl), a cationic photosensitizing agent, were examined using the P388/ADR murine leukemia, which exhibits the MDR (multidrug resistance) phe-notype, and the wild-type parent cell line, P388. The recent availability of radioactive CDSl permitted kinetic studies at drug levels in the submicromolar range. Exclusion of CDSl by P38WADR cells could be demonstrated, indicating that this agent is a substrate for the outward transport system associated with MDR. These results have implications with regard to the efficacy of cationic photosensitizers against this common neoplastic phenotype. The CDSl was readily accumulated by P388 cells and by P388/ADR cells: when the outward transport system was inhibited. Under these conditions, CDSl was tightly bound and could not be washed out even when the outward transport system was reactivated.     

A directionally sensitive hot- wire anemometer

 A new directionally sensitive velocity measurement system based upon a single oscillating hot-wire probe has been developed. The vibration of the hot-wire was effected by a piezoelectric oscillator that could be driven at different amplitudes and frequencies. The sign of the local flow velocity was determined by the phase shift between the motion and the output from the hot-wire. The system was used to measure mean and fluctuating velocities profiles of the separated flow behind a backward facing step. Received: 29 November 1995/Accepted: 26 July 1996     

STM Images of Individual Porphyrin Molecules on Cu(100) and Cu(111) Surfaces

Simply sublime! Samples of monomeric and dimeric zinc porphyrins were sublimed onto a Cu surface under ultrahigh vacuum conditions. Images obtained by scanning tunneling microscopy at room and low temperature (98 K) show features attributed to individual porphyrin molecules with excellent resolution. In the case of the (relatively large) linear dimer shown, two distinct conformations were detected on a surface with low coverage area. R=CH₂CH₂COOCH₃.     

Lutetium Texaphyrin (PCI-0123): A Near-Infrared, Water-Soluble Photosensitizer

Lutetium texaphyrin, PCI-0123, is a pure, water-soluble photosensitizer with a large broad absorption band centered at 732 nm. The compound was tested for photodynamic therapy (PDT) effectiveness in a murine mammary cancer model. The texaphyrin macrocycle as illustrated by magnetic resonance imaging and ¹⁴C-radiolabeled texaphyrin studies was shown to be tumor selective; a tumor-to-muscle ratio of 10.55 was seen after 5 h. Lutetium texaphyrin, at a drug dose of 20 μmol/kg with irradiation 5 h postinjection at 150 J/cm² and 150 mW/cm², had significant efficacy (P < 0.0001) in treating neoplasms of moderate size (40 ± 14 mm³) and also had significant efficacy ( P < 0.0001) in treating larger neoplasms (147 ± 65 mm³). The PDT efficacy was correlated with the time interval between PCI-0123 administration and light exposure. A 100% cure rate was achieved when photoirradiation took place 3 h postinjection compared to 50% for 5 h using 10 μmol/kg and 150 J/cm² at 150 mW/cm². The PDT efficacy was attributable to the selective uptakehetention of the texaphyrin photosensitizer in addition to the depth of light penetration achievable at the 732 nm laser irradiation.     

Quantitation of 17alpha-ethinylestradiol in aquatic samples using liquid-liquid phase extraction, dansyl derivatization, and liquid chromatography/positive electrospray tandem mass spectrometry

A rapid and sensitive method for the analysis of 17alpha-ethinylestradiol (EE2) in environmental aqueous samples has been developed. Aquatic samples were extracted using liquid-liquid extraction, and organic phase extracts were concentrated and derivatized with dansyl chloride. Analysis was performed using high-performance liquid chromatography with positive electrospray ionization and tandem mass spectrometry (HPLC/ESI-MS/MS). Deuterated 17alpha-ethinylestradiol was used as internal standard and was added to samples before extraction. A limit of quantitation of 1 ng/L was obtained using a 25 mL aqueous sample. The average recovery of EE2 spiked into a 25 mL tapwater sample was 100%. This highly sensitive quantitation method is useful for measuring low levels of EE2 in aqueous environmental samples.