Foscan®-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes

Maugain, Estelle; Sasnouski, Siarhei; Zorin, Vladimir; Merlin, Jean‐Louis; Guillemin, François; Bezdetnaya, Lina

doi:10.3892/or.12.3.639

Cited by 6 publications

(5 citation statements)

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“…Others have also predicted that PDT of the vasculature would be unaffected by fluence rate (10). However, the study of Iinuma et al (8) suggested that low fluence rate increased response to vascular-targeted PDT using benzoporphyrin derivative (BPD).…”

Section: Introductionmentioning

confidence: 99%

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

et al. 2010

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Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug–light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug–light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/μl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm2 significantly improved long-term tumor responses over that at 75 mW/cm2. This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm2 PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm2 PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm2 PDT provide evidence of more widespread vascular damage, which was accompanied by greater decreases in clonogenic survival. Further study of low fluence rate as a means to improve responses to PDT under conditions designed to predominantly damage vasculature is warranted.

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Section: Introductionmentioning

confidence: 99%

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

et al. 2010

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“…This is based on early PS uptake studies in animal models and patients that demonstrated maximum differential mTHPC levels in tumor vs normal tissue at 2–4 days after drug administration (15–18). However, some recent studies in murine tumor models have demonstrated a poor correlation between maximum tumor mTHPC uptake and PDT efficacy, indicating instead a better correlation with plasma mTHPC levels (19–23). This has led to the hypothesis that it is the exposure of the tumor vascular endothelial cells to the PS that determines tumor response and that this is best reflected by plasma drug concentrations (21).…”

Section: Introductionmentioning

confidence: 99%

“…With these general issues of drug transport in tumors and the particular controversy surrounding mTHPC as a background, we examined the intratumor distribution of mTHPC with respect to perfused vessels in a mouse tumor model at several time points after intravascular administration. Time points of 3 and 6 h correspond to high plasma levels of mTHPC, and 24 and 96 h correspond to high tumor mTHPC levels (20–24). We observed that at the two shorter intervals the drug concentration was higher in the vicinity of vessels and dropped significantly with distance.…”

Section: Introductionmentioning

confidence: 99%

Temporally and Spatially Heterogeneous Distribution of mTHPC in a Murine Tumor Observed by Two‐color Confocal Fluorescence Imaging and Spectroscopy in a Whole‐mount Model

Mitra

Maugain

Bolotine

et al. 2005

Photochem & Photobiology

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Efficient intratumor delivery of anticancer drugs and photosensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole-mount two-color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso-tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 mum diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.

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“…While tumor and plasma drug levels often do not correlate with PDT efficacy the Foscan concentration in leukocytes does. This indicates that leukocytes might play a role in the vascular damage process (205). For example, a detailed study of the pharmacokinetics of human tumor xenografts in mice showed that plasma levels of m THPC decrease exponentially with time while the tumor drug levels remained at maximum for 48 h. At 3 h postadministration the drug was located in the blood vessels and only later distributed in the rest of the tumor.…”

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confidence: 99%

Temoporfin (Foscan^®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer^†,‡

Senge

Brandt

2011

Photochem & Photobiology

289

218

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Foscan®-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes

Cited by 6 publications

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Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

Temporally and Spatially Heterogeneous Distribution of mTHPC in a Murine Tumor Observed by Two‐color Confocal Fluorescence Imaging and Spectroscopy in a Whole‐mount Model

Temoporfin (Foscan^®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer^†,‡

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Foscan®-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes

Cited by 6 publications

References 0 publications

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence Rate

Temporally and Spatially Heterogeneous Distribution of mTHPC in a Murine Tumor Observed by Two‐color Confocal Fluorescence Imaging and Spectroscopy in a Whole‐mount Model

Temoporfin (Foscan®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer†,‡

Contact Info

Product

Resources

About

Temoporfin (Foscan^®, 5,10,15,20‐Tetra(m‐hydroxyphenyl)chlorin)—A Second‐generation Photosensitizer^†,‡