Lutetium texaphyrin

In spite of the heavy atom, compound (32) is sufficiently fluorescent for this to be used as an analytical tool to examine localization and pharmacokinetics. In EMT-6 murine tumors, (32) localizes initially on lysosomes, with selectivity for tumor over surrounding normal tissue, and with evidence for apoptotic cell kill.137 Fluorescence studies using a hamster cheek pouch model show a maximum emission in 2-3 h, with selectivity for the tumor (x 1.5 over normal tissue) after 24 h the photosensitizer is no longer detectable.138 Lutetium texaphyrin (32) has been compared... 

Young, S.W. et al. (1996) Lutetium texaphyrin (PCI-0123) a near-infrared, water-soluble photosensitizer, Photochem. Photobiol. 63, 892-897. 

Renschler, M.F. et al. (1998) Photodynamic therapy trials with lutetium texaphyrin (Iai-Tex) in patients with locally recurrent breast cancer, Proceedings of SPIE-The International Society for Optical Engineering 3247, 35-39. 

Zellweger, M. et al. (2000) Fluorescence pharmacokinetics of Lutetium Texaphyrin (PCI-0123, Lu-Tex) in the skin and in healthy and tumoral hamster cheek-pouch mucosa, J. Photochem. Photobiol., B 55, 56-62. 

Some of this work has focused on elucidating the proposed mechanism of action of lutetium texaphyrin PCI-0123 in vitro and in vivo as well as on understanding its... 

In recent clinical and preclinical work, researchers at Pharmacyclics Inc., have demonstrated that texaphyrins selectively localize in atheromatous plaque and not in the normal aortic wall [243,300,301]. In the case of gadolinium texaphyrin PCI-0120 (3), this has been shown in human populations via MRl. With lutetium texaphyrin PCI-0123 (4), spectral bioimaging of intact rabbit aortas (i.e. after PCI-0123 injection and subsequent sacrifice) served to reveal plaque-to-normal vessel retention ratios on the order of 34 to 1 [300]. Further, extensive preclinical studies have helped establish that PCI-0123 (4) may be used in a PDT sense to effect selective photodamage of atheromatous plaque lesions in diet-induced hypercholes-terolemic New Zealand white rabbits [243,300,301]. For instance, Woodbum et al. reported that a protocol involving i.v. injection of PCI-0123 (lOpmolkg per day... 

Lutetium texaphyrin (Lu-tex) is a water-soluble, porphyrin-related molecule which has been studied as a photosensitizer in experimental models of atherosclerosis and various tumors (29). In vitro work in our laboratory revealed preferential uptake of Lu-Tex by bovine capillary endothelial cells when compared with retinal pigment epithelial cells, suggesting the possibility of increased selectivity (R. Z. Renno and J. W. Miller, unpublished data). When Lu-Tex PDT was applied to the monkey model of experimental CNV, closure of the neovascular membranes was achieved at doses of l-2mg/kg with irradiation 10-40 minutes after injection using 732nm light at 50-100 J/cm2 (30). Limited toxicity to retinal and choroidal structures, similar to that seen with verteporfin was observed. 

Arbour JD, Connolly E, Graham K, Gragoudas E, Miller JW. Photodynamic therapy of experimental choroidal neovascularization in a monkey model using intravenous infusion of lutetium texaphyrin. Invest Ophthalmol Vis Sci 1999 40(suppl) 401. 

Woodburn, K.W., Fan, Q., Kessel, D., Luo, Y., and Young, S.W. (1998) Photodynamic therapy of B16F10 murine melanoma with lutetium texaphyrin, J. Invest Dermatol., 110 746-751. 

Lutetium- texaphyrin (Lu-tex) LUTRIN ANTRIN OPTRIN Pharmacyclics Inc. 732... 

G. Kostenich, A. Orenstein, L. Roitman, Z. Malik, B. Ehrenberg (1997). In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system. J. Photochem. PhotobioL B, 39, 36-42. 

T.J. Wieman, T. Panella, R. Lustig, J. Liebmann, R. Carlson, L. Esserman, S. Dougherty, V. Fingar, D. Hoth, M. Renschler, D. Adelman (1999). Photodynamic therapy (PDT) of locally recurrent breast cancer (LRBC) with lutetium texaphyrin (lutrin) a phase IB/IIA trial. Proc. Am. Soc. Clin. Oncol., 18, 418. 

Lutetium texaphyrin PCI-0123 Lu(Tex) is a water-soluble photosensitizer with a broad absorption peak centered at 732 nm and fluorescence emission at 750 nm. Thirty-five patients with cancers metastatic to the skin or... 

Several promising photosensitisers with activation wavelengths in the far-red or near infrared regions are currently in clinical trials. The structures of several clinical PDT photosensitisers are shown in Fig. 9.3. TOOKAD, a palladium bacteriochlorophyll derivative with excitation at 763 nm is currently in phase II clinical trials for the treatment of prostate cancer (via vascular targeted PDT, vide infra). Lutetium texaphyrin (motexafin lutetium, Lutex ) which combines the advantages of water solubility, selective localisation, and the ability to be activated... 

Note Photosensitizers are as follows Photofrin , polyhematoporphyrin ethers ALA, aminolevulinic acid mTHPc, meta-tetetrahydroxyphenylchlo-rin SnET2, tin etiopurpurin, Lutetium Texaphyrin, a pendadentate aromatic metalloporphyrin BPD-MA, benzoporphyrin derivative mono acid HPPH, 2-[l-hexyloxyethyl]-devinylpyropheophorbide-a PC4, a silicon phthalocyanine AMD, age-related macular degeneration. 

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