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American Journal of Ophthalmology Mar 2000To investigate the suitability of lutetium texaphyrin (lu-tex) as a fluorescence imaging agent in the delineation of retinal vascular and choroidal vascular diseases....
PURPOSE
To investigate the suitability of lutetium texaphyrin (lu-tex) as a fluorescence imaging agent in the delineation of retinal vascular and choroidal vascular diseases. The utilization of an efficient fluorescent molecule that is also a photosensitizer represents a unique opportunity to couple diagnosis and therapy.
METHODS
Fundus fluorescence angiography comparing lu-tex (motexafin lutetium, Optrin, Pharmacyclics Inc, Sunnyvale, California) with the conventional angiographic dyes, sodium fluorescein, and indocynanine green (ICG), was performed on the eyes of normal and laser-injured New Zealand white rabbits. Plasma pharmacokinetic data and plasma protein binding were assessed in addition to light microscopy of the retina in both imaged and laser-injured eyes.
RESULTS
Normal retinal and choroidal vasculature was well delineated by lu-tex angiography. Experimentally induced choroidal and retinal vascular lesions were enhanced by lu-tex and demonstrated different staining patterns than fluorescein or ICG, particularly at the margins of the lesions. Lu-tex cleared rapidly from the plasma, with 39.7% bound to the high-density lipoprotein (HDL) fraction while 15.8% was bound to the low-density lipoprotein (LDL) fraction. No evidence of retinal toxicity after dye administration was observed by either ophthalmoscopy and fundus photography or by light microscopy.
CONCLUSION
Lu-tex angiography is a potentially valuable method for retinal vascular and choroidal vascular evaluation, and it has advantages over fluorescein and ICG angiography. The same agent could conceivably be used for both the identification of abnormal vasculature and subsequent photodynamic treatment.
Topics: Animals; Choroid; Choroidal Neovascularization; Disease Models, Animal; Fluorescein; Fluorescein Angiography; Fundus Oculi; Indocyanine Green; Lutetium; Male; Metalloporphyrins; Photochemotherapy; Photosensitizing Agents; Rabbits; Retinal Neovascularization; Retinal Vessels
PubMed: 10704552
DOI: 10.1016/s0002-9394(99)00462-6 -
Journal of Photochemistry and... Mar 1999The aim of this study is to modify the chick chorioallantoic membrane (CAM) model into a whole-animal tumor model for photodynamic therapy (PDT). By using...
Systemic application of photosensitizers in the chick chorioallantoic membrane (CAM) model: photodynamic response of CAM vessels and 5-aminolevulinic acid uptake kinetics by transplantable tumors.
The aim of this study is to modify the chick chorioallantoic membrane (CAM) model into a whole-animal tumor model for photodynamic therapy (PDT). By using intraperitoneal (i.p.) photosensitizer injection of the chick embryo, use of the CAM for PDT has been extended to include systemic delivery as well as topical application of photosensitizers. The model has been tested for its capability to mimic an animal tumor model and to serve for PDT studies by measuring drug fluorescence and PDT-induced effects. Three second-generation photosensitizers have been tested for their ability to produce photodynamic response in the chick embryo/CAM system when delivered by i.p. injection: 5-aminolevulinic acid (ALA), benzoporphyrin derivative monoacid ring A (BPD-MA), and Lutetium-texaphyrin (Lu-Tex). Exposure of the CAM vasculature to the appropriate laser light results in light-dose-dependent vascular damage with all three compounds. Localization of ALA following i.p. injections in embryos, whose CAMs have been implanted with rat ovarian cancer cells to produce nodules, is determined in real time by fluorescence of the photoactive metabolite protoporphyrin IX (PpIX). Dose-dependent fluorescence in the normal CAM vasculature and the tumor implants confirms the uptake of ALA from the peritoneum, systemic circulation of the drug, and its conversion to PpIX.
Topics: Allantois; Aminolevulinic Acid; Animals; Biological Transport; Carcinoma, Squamous Cell; Cell Division; Chick Embryo; Chorion; Female; Kinetics; Metalloporphyrins; Ovarian Neoplasms; Photosensitizing Agents; Porphyrins; Rats; Rats, Inbred F344; Tumor Cells, Cultured
PubMed: 10365445
DOI: 10.1016/S1011-1344(99)00014-7 -
Oncology (Williston Park, N.Y.) May 1999
Topics: Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Gadolinium; Humans; Lutetium; Metalloporphyrins; Photosensitizing Agents
PubMed: 10356686
DOI: No ID Found -
Lasers in Surgery and Medicine 1999New photosensitizers proposed for photodynamic therapy (PDT) treatment of tumors need to be evaluated in animal models to determine the parameters needed for treatment.... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
New photosensitizers proposed for photodynamic therapy (PDT) treatment of tumors need to be evaluated in animal models to determine the parameters needed for treatment. They also need to be compared with existing photosensitizers for efficacy. We examined the PDT response to lutetium-texaphyrin (PCI-0123) in a mouse mammary adenocarcinoma model and compared it with the PDT response seen when using Photofrin.
STUDY DESIGN/MATERIALS AND METHODS
DBA/2 mice with SMT-F tumors were used to explore PCI-0123 toxicity, laser light dose, and drug dose effects on PDT response and to determine the most effective time for light application. The PDT response of PCI-0123-treated tumors was compared with that of Photofrin-treated tumors.
RESULTS
Treatment of tumors with 150 J/cm2 of 740 nm laser light 5-6 hr after PCI-0123 administration (40 mg/kg) resulted in a 100% response rate and a 55% cure rate. Tumors treated with 150 J/cm2 of 630 nm laser light 24 hr after Photofrin administration (10 mg/kg) resulted in a 67% response rate and a 16% cure rate.
CONCLUSION
PCI-0123 was found to be a more effective photosensitizer than Photofrin.
Topics: Adenocarcinoma; Animals; Dihematoporphyrin Ether; Female; Laser Therapy; Mammary Neoplasms, Animal; Metalloporphyrins; Mice; Mice, Inbred DBA; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured
PubMed: 10327046
DOI: 10.1002/(sici)1096-9101(1999)24:4<276::aid-lsm5>3.0.co;2-n -
Lasers in Surgery and Medicine 1998Three prototype microchannel-cooled stacked diode array lasers were compared with the currently used conventional argon ion laser-pumped tunable dye lasers for... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
Three prototype microchannel-cooled stacked diode array lasers were compared with the currently used conventional argon ion laser-pumped tunable dye lasers for suitability as light sources in photodynamic therapy (PDT) treatment.
STUDY DESIGN/MATERIALS AND METHODS
The PDT response of Chinese hamster ovary (CHO-K1) cells in culture and SMT-F tumor bearing mice treated with chloro-aluminum sulfonated phthalocyanin (CASPc), benzoporphyrin derivative mono-acid (BPD-MA), and lutetium texaphyrin (Lutex) was determined using each laser light source. Survival of the CHO cells was measured using a cloning assay. Tumor regression/eradication was used to assess response in the mice.
RESULTS
Both sources of laser light produced comparable PDT responses in the two systems tested.
CONCLUSION
It would be possible to replace the currently used argon ion laser-pumped dye laser systems with the diode lasers tested.
Topics: Animals; Cell Line; Cricetinae; Drug Screening Assays, Antitumor; Female; In Vitro Techniques; Indoles; Laser Therapy; Lutetium; Metalloporphyrins; Mice; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Experimental; Organometallic Compounds; Ovary; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 9888323
DOI: 10.1002/(sici)1096-9101(1998)23:5<274::aid-lsm7>3.0.co;2-o -
The Journal of Investigative Dermatology May 1998Photodynamic therapy (PDT) of pigmented melanoma has generally been unsuccessful because of insufficient light penetration in such tissues. In this study, the...
Photodynamic therapy (PDT) of pigmented melanoma has generally been unsuccessful because of insufficient light penetration in such tissues. In this study, the responsiveness of the heavily pigmented B16F10 murine melanoma to lutetium texaphyrin (PCI-0123), a water-soluble sensitizer with strong absorbance in the near infrared (700-760 nm), was examined. These studies were carried out in both normal and ApoE deficient C57BL/6 mice. The latter strain exhibits a lipoprotein profile more like humans (low density lipoprotein > high density lipoprotein) than rodents (high density lipoprotein >> low density lipoprotein). Under optimal conditions of drug dose, light dose, and interval between drug administration and irradiation--the median survival time of C57BL/6 tumor bearing mice was approximately doubled (29 d) compared with tumor bearing control animals (13 d). The life-span of the ApoE knockout mice was greater (33 d) than the C57BL/6 animals (23 d) when irradiation occurred 3 h after administration of a 10 micromol per kg drug dose. The greater efficacy of PDT in the ApoE deficient mice was associated with more rapid clearance of drug from the blood, greater accumulation of sensitizer in tumor tissue, and substantially greater drug binding to the very low density lipoprotein/low density lipoprotein plasma fraction. Confocal laser scanning microscopy showed that the predominant subcellular site of photosensitizer binding was to melanosomes; costaining was performed with Mel-5. Melanosomes are susceptible to oxidative stress. Photo-oxidation, mediated by PCI-0123 PDT, could potentially overload an already highly oxidized stressed state leading to cell death. The good tissue penetration depth achieved by PCI-0213 mediated PDT and the activation of melanosomes makes PDT of pigmented melanoma, for the first time, clinically relevant.
Topics: Animals; Apolipoproteins E; Apoptosis; Blood Proteins; Female; Longevity; Melanoma; Metalloporphyrins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Tissue Distribution
PubMed: 9579539
DOI: 10.1046/j.1523-1747.1998.00182.x -
Journal of Photochemistry and... May 1997An in vivo fluorescence monitoring and photodynamic therapy (PDT) study was performed using the new photosensitizer lutetium texaphyrin (Lu-Tex). This photosensitizer is... (Comparative Study)
Comparative Study
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 > or = PII > Chl, PII > ALA > Lu-Tex > Chl and PII > Lu-Tex > ALA > Chl respectively.
Topics: Animals; Dihematoporphyrin Ether; Female; Foot; Lasers; Lutetium; Metalloporphyrins; Mice; Mice, Inbred BALB C; Molecular Structure; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Solubility; Spectrometry, Fluorescence; Water
PubMed: 9210320
DOI: 10.1016/s1011-1344(96)00005-x -
Photochemistry and Photobiology Mar 1997Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light. The sensitizer is highly...
Lutetium texaphyrin (PCI-0123) is a pure, water-soluble photodynamic therapy (PDT) agent that is activated by tissue-penetrating far red light. The sensitizer is highly fluorescent and exhibits a strong, broad emission signal at 750 nm. In vitro cellular uptake studies revealed an increase in sensitizer retention with incubation time. Confocal laser scanning microscopy demonstrated that the intracellular localization site of PCI-0123 is the lysosomes. Ensuing illumination of the EMT6 cells led to lysosomal breakup, extensive cytoplasmic blebbing and subsequent cell death. Noninvasive spectral imaging analysis of PCI-0123 fluorescence depicted selective drug uptake, compared to surrounding normal tissue, in EMT6 mammary sarcomas syngeneic to BALB/c mice. The PCI-0123 PDT was shown to effectively treat the EMT6 murine sarcoma. Irradiation (732 nm light) 3 h postintravenous injection of 10 mumol PCI-0123 per kg gave 100% cures (no evidence of cancer), whereas light exposure at 5 h resulted in 75% cures. Hematoxylin and eosin histologic examination of photoirradiated tumors indicated apoptosis of the EMT6 neoplasms at early times post-PDT progressing, with time, to extensive necrotic areas. Gel electrophoresis of extracted photoirradiated tumors showed the typical apoptotic DNA ladder pattern that increased in intensity following PDT treatment.
Topics: Animals; Mammary Neoplasms, Experimental; Metalloporphyrins; Mice; Microscopy, Confocal; Photochemotherapy; Photosensitizing Agents; Sarcoma, Experimental; Subcellular Fractions; Tumor Cells, Cultured
PubMed: 9077121
DOI: 10.1111/j.1751-1097.1997.tb08579.x -
Journal of Clinical Laser Medicine &... Oct 1996Cancer and cardiovascular disease are the leading causes of death in the western world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of... (Comparative Study)
Comparative Study
Cancer and cardiovascular disease are the leading causes of death in the western world. Photodynamic therapy (PDT) has demonstrated activity in the treatment of superficial cancerous lesions and as an intraoperative adjunct during surgical debulking. Texaphyrins are pure, synthetic water-soluble macrocycles that localize in both cancerous lesions and atheromatous plaque. Lutetium texaphyrin (PCI-0123) is activated by tissue-penetrating far red light (720-760 nm). Patient diagnosis and treatment planning is possible via magnetic resonance imaging (MRI) with the paramagnetic gadolinium texaphyrin (PCI-0120) or via fluorescence imaging using the diamagnetic PCI-0123. In this study it is shown that texaphyrins localize selectively in cancer and atheromatous plaque. PDT with PCI-0123 is found to cause selective photodamage to the diseased tissue. Specifically, PCI-0123 acts to eradicate the SMT-F murine mammary tumors and diet-induced atheromatous plaque in rabbits.
Topics: Animals; Antineoplastic Agents; Argon; Arteriosclerosis; Cholesterol; Gadolinium; Laser Therapy; Lutetium; Male; Metalloporphyrins; Mice; Mice, Inbred DBA; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Rabbits; Survival Analysis; Tumor Cells, Cultured
PubMed: 9612202
DOI: 10.1089/clm.1996.14.343 -
AIDS Patient Care and STDs Jun 1996
Clinical Trial
Topics: Acquired Immunodeficiency Syndrome; Female; Humans; Injections, Intravenous; Lighting; Lutetium; Male; Metalloporphyrins; Neoplasms; Photochemotherapy; Photosensitizing Agents; Sarcoma, Kaposi
PubMed: 11361635
DOI: No ID Found