In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system

doi:10.1016/S1011-1344(96)00005-X

Journal of Photochemistry and Photobiology B: Biology

Volume 39, Issue 1, May 1997, Pages 36-42

https://doi.org/10.1016/S1011-1344(96)00005-X Get rights and content

Abstract

An in vivo fluorescence monitoring and photodynamic therapy (PDT) study was performed using the new photosensitizer lutetium texaphyrin (Lu-Tex). This photosensitizer is water soluble and has the additional advantage of strong absorption near 730 nm. C26 colon carcinoma was transplanted in the foot of BALB/c mice. In vivo fluorescence spectroscopy was applied to study Lu-Tex tissue distribution kinetics. For this purpose, fluorescence intensity both in the foot with the tumor and in the normal foot was measured in vivo by the laser-induced fluorescence (LIF) system. For PDT, both feet of the mice were irradiated simultaneously with the use of a new high intensity pulsed light delivery system, the Photodyne. The results of the LIF measurements showed that the maximal fluorescence intensity ratio between the normal and tumor bearing foot (FIR) was observed 24–48 h after the agent injection. Photoirradiation with doses from 90 to 240 J cm⁻² (0.6 J cm⁻² per 2 ms pulse, 1 Hz) 24 h after injection of Lu-Tex at a dose of 10 mg kg⁻¹ caused significant tumor necrosis and delay in the tumor growth rate. The antitumor effect was enhanced with increasing light doses. Normal tissue response to PDT with Lu-Tex was determined as the damage index of the normal foot, which was irradiated simultaneously with the tumor bearing foot. The normal tissue response after PDT with Lu-Tex was compared with 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PP), chlorin e₆ (Chl) and Photofrin (PII) at the same values of antitumor effect. The results showed that at 50, 80 and 100% inhibition of tumor growth the orders of the values of normal foot damage indexes were as follows: ALA > Lu-Tex ≥ PII > Chl, PII > ALA > Lu-Tex > Chl and PII > Lu-Tex > ALA > Chl respectively.

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Biolocalisation and photochemical properties of novel macrocyclic photosensitisers, guanidiniocarbonyl-substituted tetraphenylporphyrin (1) and sugar-substituted sapphyrin (2) were investigated by spectroscopic methods. Both photosensitisers absorb in far visible region and showed good tumour localisation. Photosensitiser 2 demonstrated significantly larger absolute and relative to normal tissue (T/N) amount in tumour (330 μg g⁻¹ wet tissue, T/N=19.0) than photosensitiser 1 did (13 μg g⁻¹ wet tissue, T/N=2.1). According to iodometric and uric acid assays, compound 1 produced large amount of ¹O₂ (Φ_Δ=0.60–0.68), while compound 2 showed non-significant ¹O₂ production (Φ_Δ=0.04). The electronic spectroscopic study confirms that only photosensitiser 1 is able to mediate photooxidation of model compounds (BSA, poly(Trp), Tyr, Trp, and GMP) after light irradiation. Pour photochemical activity of compound 2 was explained by its self-aggregation. Raman spectroscopic study indicated that monomerised photosensitiser 2 effectively damaged BSA and calf thymus DNA after light excitation at the conditions of high excess of these macromolecules.
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We present new HPLC methods for the quantitation in human plasma of two investigative metallotexaphyrin agents, motexafin gadolinium (Gd-Tex) and motexafin lutetium (Lu-Tex). Each assay uses: the other texaphyrin analogue as an internal standard; protein precipitation with acetonitrile:methanol (50:50, v/v); an ODS reversed-phase column; an isocratic mobile phase of 100 mM ammonium acetate, pH 4.3:acetonitrile:methanol (59:21:20, v/v/v); and absorbance detection at 470 nm. The Gd-Tex assay has a lower limit of quantitation (LLOQ) of 0.01 μM and is linear between 0.01and 30 μM. The Lu-Tex assay has an LLOQ of 0.1 μM and is linear between 0.1 and 30 μM. The assays are suited for in vivo preclinical studies and clinical trials because they require minimal amounts of plasma, are sensitive, and involve a 30-min run time. These assays are important tools for evaluating the potential of Gd-Tex and Lu-Tex as a radiation enhancer and photosensitizer, respectively.
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Regular paperIn vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system

Abstract

J. Photochem. Photobiol. B: Biol.

J. Photochem. Photobiol. B: Biol.

Preclinical examination of first and second generation of photosensitizers used in photodynamic therapy Photochem

Photobiol.

Synthesis and structural characterization of lanthanide (III) texaphyrins

Inorg. Chem.

Methallotexaphyrins: a new family of photosensitizes for efficient generation of singlet oxygen

J. Chem. Soc. Chem. Commun.

Tripyrroledimethine-derived (Texaphyrin type) macrocycles: potential photosensitizers which absorb in the far red spectral region

SPIE 1426

The binding and photosensitization effects of tetrabenzoporphyrins and texaphyrin in bacterial cells

Lasers Med. Sci.

Regular paper
In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system