Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice

Richter, Anna; Cerruti-Sola, S.; Sternberg, Ethan D.; Dolphin, David; Levy, Julia G.

doi:10.1016/1011-1344(90)80008-l

Cited by 125 publications

(73 citation statements)

References 10 publications

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“…Overall, the data from our studies and the previous work in the rabbit models demonstrate that vascular damage after PDT is greater in animals given light treatment at short intervals after BPD injection. These data are consistent with measurements of tissue levels of BPD in highly vascularized structures of the rabbit eye such as the cilliary body and choroid where the highest BPD levels were observed 5 min after photosensitizer injection (Haimovici et al, 1997) and the rapid distribution of BPD into murine tissues after injection (Richter et al, 1990.…”

Section: Discussionsupporting

confidence: 79%

“…The predominance of vascular damage in treated tissues correlates well with the high serum levels of photosensitizer that are present at short times after drug injection. Light treatment is generally given within 3 h of drug injection because of the rapid pharmacokinetics of BPD in tissue (Richter et al, 1990). Tissue microvasculature is an important target for PDT using several photosensitizers (Henderson and Farrell, 1989;Fingar et al, 1992) and direct damage to cells in the vessel wall including endothelial cells, and damage to blood components, including platelets, has been observed (Henderson and Dougherty, 1992).…”

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confidence: 99%

“…This agent is chemically pure and is activated with light at long wavelengths (690 nm) which allows theoretically for deeper penetration of light into the treatment area. Benzoporphyrin derivative has rapid plasma and tissue pharmacokinetics and is thus quickly cleared from tissues, resulting in a diminished period of skin photosensitivity compared to other drugs including Photofrin (Richter et al, 1990;Levy et al, 1993). A wide range of diseases are under investigation for treatment with PDT using BPD including solid tumours , choroidal neovascularization (Lin et al, 1994), arthritis (Chowdary, 1994), HIV therapy (North et al, 1996) and uterine endometrial ablation (Wyss et al, 1994).…”

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confidence: 99%

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Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

et al. 1999

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Summary Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg -1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm -2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction.

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Section: Discussionsupporting

confidence: 79%

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confidence: 99%

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confidence: 99%

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Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

et al. 1999

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“…The latter property is receiving increasing attention since a rapid elimination of the photosensitiser from the organism is likely to minimise the onset of undesired side effects, including the persistent skin photosensitivity which has been observed for some PDT-treated patients (Marcus, 1992). Actually, some second-generation PDT agents, such as N-aspartyl-chlorin e 6 (Ferrario et al, 1992) and benzoporphyrin derivative (Richter et al, 1990), yield significant tumour concentrations at 3-4 hr after administration and are completely cleared from the organism in a few days.To obtain further information on the relationship between the physico-chemical characteristics of a photosensitiser and its affinity for tumours, we studied the pharmacokinetic properties of a series of porphycenes with programmed changes in their chemical structure, which had been synthesised with a high purity by Vogel et al (1987). Porphycenes are electronic isomers of porphine characterised by an envelope of three absorption bands in the red region, whose molar extinction coefficient is about 10-fold larger than that measured for haematoporphyrin derivatives.…”

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confidence: 99%

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Effect of chemical structure and hydrophobicityon the pharmacokinetic properties of porphycenes in tumour-bearing mice

et al. 1997

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The efficiency and selectivity of tumour targeting by several tetra-n-propylporphycene (TPPn) and tetrakis(methoxyethyl-)porphycene (TMPn) derivatives have been studied by administering 3.76 mmol/kg of aqueous or liposomal porphycene formulations to BALB/c mice bearing an i.m. implanted MS-2 fibrosarcoma. These 2 parameters have been studied as a function of the type of substituents linked to the 9-position of the macrocycle by amide, ester or ether functional groups. The pharmacokinetic properties appear to be controlled mainly by the degree of porphycene hydrophobicity, as evaluated by measuring their retention times in a C 18 column for HPLC. Thus, the post-injection time (T 50 ) at which the porphycene concentration in the plasma decreases to 50% of the initial value ranged from a few minutes for the less hydrophobic to several hours for the more hydrophobic porphycenes. An increase in hydrophobicity also was accompanied by an enhanced efficiency and selectivity of tumour targeting. The less hydrophobic porphycenes showed a maximum tumour uptake of 0.5-2 nmol/g of tissue at 10-20 min after administration with a tumour/peri-tumoural concentration ratio around 2-3, while those with higher hydrophobicity reached tumour concentrations of 7-8 nmol/g at 24-48 hr after administration with concentration ratios higher than 20. In the past few years, several photosensitisers, mainly belonging to the porphyrin class or analogues thereof, have been proposed as phototherapeutic agents for tumours, and a few of them are now registered for clinical use or are in phase II/III clinical trials. This modality is usually termed ''photodynamic therapy'' (PDT) and can be potentially extended to the treatment of some nononcological diseases (Levy and Obochi, 1996). In spite of such intensive research and promising developments, the factors which control the efficiency and the rate of photosensitiser accumulation in tumour and normal tissues are only partially understood.The data obtained through a variety of pharmacokinetic investigations with Photofrin II, a mixture of several haematoporphyrinrelated compounds which has been so far most frequently used in pre-clinical and clinical PDT, appear to indicate that the tumourlocalising activity is particularly large for some oligomeric components endowed with a marked degree of hydrophobicity (Marcus, 1992). This conclusion received further support from different lines of evidence: (i) the affinity of sulphonated porphyrins (Kessel et al., 1987) and phthalocyanines (Peng et al., 1991) for experimental tumours was found to increase upon decreasing the number of sulphonate groups, hence with decreasing hydrophilicity; (ii) the efficiency of tumour targeting by a series of haematoporphyrin diesters increased with the increasing length of the esterifying hydrocarbon chains (Berg et al., 1993), and similar results were obtained with some Ge(IV)-phthalocyanines bearing different hydrocarbon axial ligands to the metal ion (Soncin et al., 1995); (iii) incorporation of the photosensitiser into ...

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Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration

Schmidt‐Erfurth¹

1999

Arch Ophthalmol

305

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To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in agerelated macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. Design: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m 2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm 2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm 2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2-or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. Results: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after

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Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice

Cited by 125 publications

References 10 publications

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

Effect of chemical structure and hydrophobicityon the pharmacokinetic properties of porphycenes in tumour-bearing mice

Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration

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