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Methods and Findings in Experimental... Mar 2005Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from...
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole.
Topics: Clinical Trials as Topic; Humans
PubMed: 15834466
DOI: No ID Found -
Circulation Sep 2003Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells.... (Clinical Trial)
Clinical Trial
Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.
BACKGROUND
Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment.
METHODS AND RESULTS
An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy.
CONCLUSIONS
This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.
Topics: Adult; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Metalloporphyrins; Middle Aged; Photochemotherapy; Photosensitizing Agents; Stents; Treatment Outcome
PubMed: 12939212
DOI: 10.1161/01.CIR.0000087602.91755.19 -
Photochemistry and Photobiology Jan 2003The optical properties (absorption [mu(a)], transport scattering [mu('s)] and effective attenuation [mu(eff)] coefficients) of normal canine prostate were measured in...
The optical properties (absorption [mu(a)], transport scattering [mu('s)] and effective attenuation [mu(eff)] coefficients) of normal canine prostate were measured in vivo using interstitial isotropic detectors. Measurements were made at 732 nm before, during and after motexafin lutetium (MLu)-mediated photodynamic therapy (PDT). They were derived by applying the diffusion theory to the in vivo peak fluence rates measured at several distances (3, 6, 9, 12 and 15 mm) from the central axis of a 2.5 cm cylindrical diffusing fiber (CDF). Mu(a) and mu('s) varied between 0.03-0.58 and 1.0-20 cm(-1), respectively. Mu(a) was proportional to the concentration of MLu.Mu(eff) varied between 0.33 and 4.9 cm(-1) (mean 1.3 +/- 1.1 cm(-1)), corresponding to an optical penetration depth (8 = 1/(mu(eff)) of 0.5-3 cm (mean 1.3 +/- 0.8 cm). The mean light fluence rate at 0.5 cm from the CDF was 126 +/- 48 mW/cm2 (N = 22) when the total power from the fiber was 375 mW (150 mW/cm). This study showed significant inter- and intraprostatic differences in the optical properties, suggesting that a real-time dosimetry measurement and feedback system for monitoring light fluences during treatment should be advocated for future PDT studies. However, no significant changes were observed before, during and after PDT within a single treatment site.
Topics: Animals; Dogs; Light; Male; Metalloporphyrins; Optics and Photonics; Photochemotherapy; Photosensitizing Agents; Prostate
PubMed: 12856887
DOI: 10.1562/0031-8655(2003)077<0081:ivopon>2.0.co;2 -
Clinical Cancer Research : An Official... Mar 2001Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to...
Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to evaluate the toxicity and tissue effects associated with this treatment. Twenty-five adult male beagles with normal prostate glands were given an i.v. injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An additional two dogs were used as controls and did not receive any photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate. Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was delivered interstitially and/or transurethrally to the prostate via cylindrical diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All subjects were monitored for clinical evidence of toxicity. Specimens were examined macroscopically and microscopically to characterize the tissue reaction and assess extent of tissue effect as a result of treatment. Interstitial and/or transurethral PDT were successfully delivered in all dogs with no perioperative complications. No clinical evidence of acute urinary obstruction or rectal bleeding was noted. At all dose levels, macroscopic and microscopic evaluation revealed a prostatic tissue reaction characterized initially (within 48 h) by inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. Comprehensive treatment of the entire prostate could be achieved using the interstitial alone approach or combined transurethral and interstitial approach. The transurethral alone approach did not result in complete coverage of the prostate. Dogs receiving transurethral or combined interstitial and transurethral treatment developed erythema and urethral epithelial disruption at all dose levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6 mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated with the interstitial alone approach were found to have the least amount of urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT is feasible using an interstitial alone or combined interstitial and transurethral approach. The interstitial alone technique results in the least amount of toxicity. The prostatic tissue reaction to treatment is characterized by initial inflammation and necrosis followed by fibrosis and glandular epithelial atrophy.
Topics: Animals; Dogs; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Endoscopy; Light; Male; Metalloporphyrins; Necrosis; Photosensitizing Agents; Phototherapy; Prostate; Prostatic Neoplasms; Time Factors; Urinary Bladder
PubMed: 11297261
DOI: No ID Found -
World Journal of Urology Oct 2010Although in early stages of clinical development, photodynamic therapy (PDT) shows promise in delivering focal treatment of both primary and post-radiotherapy prostate... (Review)
Review
Although in early stages of clinical development, photodynamic therapy (PDT) shows promise in delivering focal treatment of both primary and post-radiotherapy prostate cancer. This article will review the mechanism of action of PDT, previous research using PDT for treating prostate cancer including the development of newer vascular-acting photosensitizers, and the potential advantages and disadvantages of PDT in delivering focal therapy.
Topics: Dihematoporphyrin Ether; Humans; Male; Mesoporphyrins; Metalloporphyrins; Photochemotherapy; Photosensitizing Agents; Prostatic Neoplasms; Treatment Outcome
PubMed: 20454966
DOI: 10.1007/s00345-010-0554-2 -
Journal of Biomedical Optics 2007Near-infrared diffuse reflectance spectroscopy (DRS) has been used to noninvasively monitor optical properties during photodynamic therapy (PDT). This technique has been... (Comparative Study)
Comparative Study
Near-infrared diffuse reflectance spectroscopy (DRS) has been used to noninvasively monitor optical properties during photodynamic therapy (PDT). This technique has been extensively validated in tissue phantoms; however, validation in patients has been limited. This pilot study compares blood oxygenation and photosensitizer tissue uptake measured by multiwavelength DRS with ex vivo assays of the hypoxia marker, 2-(2-nitroimida-zol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5), and the photosensitizer (motexafin lutetium, MLu) from tissues at the same tumor site of three tumors in two patients with intra-abdominal cancers. Similar in vivo and ex vivo measurements of MLu concentration are carried out in murine radiation-induced fibrosarcoma (RIF) tumors (n=9). The selection of optimal DRS wavelength range and source-detector separations is discussed and implemented, and the association between in vivo and ex vivo measurements is examined. The results demonstrate a negative correlation between blood oxygen saturation (StO(2)) and EF5 binding, consistent with published relationships between EF5 binding and electrode measured pO(2), and between electrode measured pO(2) and StO(2). A tight correspondence is observed between in vivo DRS and ex vivo measured MLu concentration in the RIF tumors; similar data are positively correlated in the human intraperitoneal tumors. These results further demonstrate the potential of in vivo DRS measurements in clinical PDT.
Topics: Algorithms; Animals; Computer Simulation; Fibrosarcoma; Humans; Metalloporphyrins; Mice; Mice, Inbred C3H; Models, Biological; Oxygen; Reproducibility of Results; Sensitivity and Specificity; Spectrophotometry, Infrared
PubMed: 17614731
DOI: 10.1117/1.2743082 -
Current Opinion in Ophthalmology Jun 2001Photodynamic therapy uses a photoactivating agent to selectively treat choroidal neovascularization. In April 2000, the United States Food and Drug Administration... (Review)
Review
Photodynamic therapy uses a photoactivating agent to selectively treat choroidal neovascularization. In April 2000, the United States Food and Drug Administration approved verteporfin photodynamic therapy for the treatment of subfoveal, predominately classic, choroidal neovascularization caused by age-related macular degeneration. The treatment of choroidal neovascularization from other causes such as myopia, angioid streaks, and idiopathy, and presumed ocular histoplasmosis syndrome is still under investigation. Other photoactivating agents are being evaluated. Photodynamic therapy has been shown to halt the progression of visual loss in patients with age-related macular degeneration who have subfoveal predominately classic choroidal neovascularization. The socio-economic impact of verteporfin approval has yet to be determined.
Topics: Choroidal Neovascularization; Humans; Macular Degeneration; Metalloporphyrins; Photochemotherapy; Photosensitizing Agents; Porphyrins; Verteporfin
PubMed: 11389347
DOI: 10.1097/00055735-200106000-00010 -
Advanced Drug Delivery Reviews Oct 2001The present review examines the importance of improving photosensitizer delivery for choroidal neovascularization (CNV) in light of the clinical impact of photodynamic... (Review)
Review
The present review examines the importance of improving photosensitizer delivery for choroidal neovascularization (CNV) in light of the clinical impact of photodynamic therapy (PDT) for CNV. An overview of the classes of available photosensitizers is provided and the properties governing photosensitizer uptake and circulation in serum are discussed. Current delivery systems, for example liposomal formulations as well as the use of the promising strategy of antibody targeted delivery as a strategy to improve PDT selectivity and efficiency for CNV treatment are described. A summary of the work using Verteporfin, tin ethyl purpurin and Lu-Tex--photosensitizers currently in clinical trials for CNV--is given.
Topics: Choroidal Neovascularization; Clinical Trials as Topic; Humans; Liposomes; Metalloporphyrins; Photochemotherapy; Photolysis; Photosensitizing Agents; Porphyrins; Verteporfin
PubMed: 11672876
DOI: 10.1016/s0169-409x(01)00195-8 -
Circulation Nov 2000Motexafin lutetium (Lu-Tex) is a photosensitizer that targets atheromatous plaque. Subsequent photoactivation (photodynamic therapy [PDT]) induces local cytotoxic...
BACKGROUND
Motexafin lutetium (Lu-Tex) is a photosensitizer that targets atheromatous plaque. Subsequent photoactivation (photodynamic therapy [PDT]) induces local cytotoxic effects. The aim of the present study was to investigate whether Lu-Tex targets vein graft intimal hyperplasia and whether subsequent photoactivation attenuates the disease process.
METHODS AND RESULTS
The subcellular localization of Lu-Tex and postillumination viability were studied in cultured human vein graft smooth muscle cells. Inferior vena cava-grafted rats were injected with Lu-Tex (10 mg/kg) 4 or 12 weeks after grafting. Biodistribution was assessed in a subgroup 24 hours after administration. Light therapy (742 nm) was performed 24 hours after Lu-Tex injection by illuminating intraperitoneally placed isografts using a laparotomy. Animals were divided into the following 4 groups: PDT (n=15), Lu-Tex injection and laparotomy (n=13), light treatment (n=14), and laparotomy only (n=13). Grafts were harvested 14 days after treatment for histochemical analysis. Lu-Tex localized within subcellular organelles of smooth muscle cells, and subsequent photoactivation induced cell death via apoptosis. The Lu-Tex concentrations present in the vein grafts were 9.3 times higher than those in the normal inferior vena cava. Postoperative PDT at 4 weeks after surgery significantly reduced the intima/media ratio, whereas treatment at 12 weeks did not reduce the intima/media ratio. Activated macrophages were observed 4 weeks after grafting; however, a significant reduction occurred in these cells by 12 weeks. The mechanism by which PDT works may be related to the presence of activated macrophages.
CONCLUSIONS
PDT significantly reduces the intima/media ratio in the early phase of vein graft disease. Lu-Tex-mediated PDT may be a viable method for the attenuation of atherosclerotic disease in vein grafts.
Topics: Animals; Antigens, Differentiation; Cells, Cultured; Graft Occlusion, Vascular; Humans; Hyperplasia; Laparotomy; Light; Macrophages; Metalloporphyrins; Muscle, Smooth, Vascular; Photochemotherapy; Photosensitizing Agents; Rats; Tissue Distribution; Transplantation, Isogeneic; Tunica Intima; Vena Cava, Inferior
PubMed: 11082401
DOI: 10.1161/01.cir.102.suppl_3.iii-275 -
Journal of Photochemistry and... Jun 2005It is desirable to quantify the distribution of the light fluence rate, the optical properties, the drug concentration, and the tissue oxygenation for photodynamic... (Clinical Trial)
Clinical Trial
Determination of the distribution of light, optical properties, drug concentration, and tissue oxygenation in-vivo in human prostate during motexafin lutetium-mediated photodynamic therapy.
It is desirable to quantify the distribution of the light fluence rate, the optical properties, the drug concentration, and the tissue oxygenation for photodynamic therapy (PDT) of prostate cancer. We have developed an integrated system to determine these quantities before and after PDT treatment using motorized probes. The optical properties (absorption (micro(a)), transport scattering (micro(s'), and effective attenuation (micro(eff)) coefficients) of cancerous human prostate were measured in-vivo using interstitial isotropic detectors. Measurements were made at 732 nm before and after motexafin lutetium (MLu) mediated PDT at different locations along each catheter. The light fluence rate distribution was also measured along the catheters during PDT. Diffuse absorption spectroscopy measurement using a white light source allows extrapolation of the distribution of oxygen saturation StO2, total blood volume ([Hb]t), and MLu concentration. The distribution of drug concentration was also studied using fluorescence from a single optical fiber, and was found to be in good agreement with the values determined by absorption spectroscopy. This study shows significant inter- and intra-prostatic variations in the tissue optical properties and MLu drug distribution, suggesting that a real-time dosimetry measurement and feedback system for monitoring these values during treatment should be considered in future PDT studies.
Topics: Dose-Response Relationship, Drug; Drug Monitoring; Humans; Light; Male; Metalloporphyrins; Optics and Photonics; Oxygen; Photochemotherapy; Prostatic Neoplasms; Spectrophotometry
PubMed: 15896650
DOI: 10.1016/j.jphotobiol.2004.09.013