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P S Haydon

Publications and source records attributed to P S Haydon.

7 recordsLinked to original sources
PubMed1999

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

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.

Animals↗
PubMed1998

In vivo and in vitro photodynamic studies with benzochlorin iminium salts delivered by a lipid emulsion.

Benzochlorin iminium salts (BIs) are hydrophobic photosensitizers based on an octaethylbenzochlorin nucleus that absorb in the near-IR region of the visible spectrum. In these studies the photodynamic activities of the zinc, copper and metal-free BI derivatives were compared in vivo in C3H-HeJ mice bearing a mammary adenocarcinoma tumor line. In vitro studies were also performed with the radiation-induced fibrosarcoma tumor line. An argon-pumped Ti-sapphire laser tuned to deliver light between 710 and 800 nm or an Oriel arc-lamp filtered to deliver broadband light above 590 nm were used as light source. A lipid emulsion was used as the delivery system for sensitizers in all studies. A pronounced solvent dependence was observed for the Q band for each of all iminium salts examined. As an example, the metal-free (BI) derivative had an absorption maximum at 798 nm in dichloromethane and at 727 nm in serum. The action spectra showed a greater PDT response at blue-shifted wavelengths for each of the three iminium salts both in vivo and in vitro. Among the three derivatives, the zinc analog (ZnBI) produced the greatest tumor regression at the low drug/light dose of 0.7 (mumole/kg and 200 J/cm2. These results indicate that iminium salts have characteristics that may make them promising third-generation photosensitizers.

Adenocarcinoma↗
PubMed1997

Photodynamic therapy using a protoporphyrinogen oxidase inhibitor.

The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway. Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a protoporphyrinogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX. Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, the duration of inhibitor exposure to animals, and the amount of light used in PDT. Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis. Tumor cure in animals given 4000 ppm FP-846 in feed for 3 days and 300 J/cm2 602-670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).

Animals↗
PubMed1997

The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using photofrin.

Several studies have reported thrombus formation and/or the release of specific vasoactive eicosanoids, suggesting that platelet activation or damage after photodynamic therapy (PDT) may contribute to blood flow stasis. The role of circulating platelets on blood flow stasis and vascular leakage of macromolecules during and after PDT was assessed in an intravital animal model. Sprague-Dawley rats bearing chondrosarcoma on the right hind limb were injected intravenously (i.v.) with 25 mg/kg Photofrin 24 h before light treatment of 135 J/cm2 at 630 nm. Thrombocytopenia was induced in animals by administration of 3.75 mg/kg of rabbit anti-rat platelet antibody i.v. 30 min before the initiation of the light treatment. This regimen reduced circulating platelet levels from 300,000/mm3 to 20,000/mm3. Reductions in the luminal diameter of the microvasculature in normal muscle and tumor were observed in control animals given Photofrin and light. Venule leakage of macromolecules was noted shortly after the start of light treatment and continued throughout the period of observation. Animals made thrombocytopenic showed none of these changes after PDT in either normal tissues or tumor. The lack of vessel response correlated with the absence of thromboxane release in blood during PDT. These data suggest that platelets and eicosanoid release are necessary for vessel constriction and blood flow stasis after PDT using Photofrin.

Animals↗
PubMedDate not supplied

Vascular damage after photodynamic therapy of solid tumors: a view and comparison of effect in pre-clinical and clinical models at the University of Louisville.

Microvascular damage that results in blood flow stasis is a frequent consequence of photodynamic therapy. The magnitude of this response is dependent on the type of photosensitizer employed for treatment, the amount of drug and light used in therapy and the time period between drug injection and treatment. This review highlights the mechanisms that lead to blood flow stasis in tumor and normal tissues and discusses methods to increase the selectivity of vascular response.

Animals↗