Tin Ethyl Etiopurpurin Research Articles

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The treatment of disease by highly reactive oxygen intermediates generated through the interaction of light with a photosensitizer is called photodynamic therapy (PDT). Intensive research on PDT was initiated in the mid-1970s by Dougherty's group in Buffalo16 and culminated in the approval by the Food and Drug Administration of PDT with porfimer sodium and laser light in 1995. For a review of the history of PDT, see references 11 and 44.In PDT, patients are first administered a photosensitizer followed by exposure of treatment sites to light. There are several photosensitizers that have been used in dermatology including hematoporphyrin derivative (HPD), porfimer sodium (Photofrin, which is a purified version of hematoporphyrin derivative), 5-aminolevulinic acid (ALA), benzoporphyrin derivative (BPD, verteporfin), tin ethyl etiopurpurin (SnET2), and monoaspartyl chlorin e6. In North America, none of these photosensitizers has yet received regulatory approval for treating skin disorders, although porfimer sodium has been approved in several countries, including the United States and Canada, for the treatment of certain pulmonary, gastrointestinal, and genitourinary malignancies. This review focuses on the use of PDT in dermatology. Although similar in principle, PUVA therapy and extracorporeal photopheresis are not discussed.

Interstitial Photodynamic Therapy of the Canine Prostate Using Intra-Arterial Administration of Photosensitizer and Computerized Pulsed Light Delivery

We determined the feasibility of complete treatment of the canine prostate and long-term effectiveness of interstitial photodynamic therapy using the intra-arterial photosensitizer QLT0074 (benzoporphyrin derivative 1,3-diene C,D-diethylene glycol ester A ring) (QLT, Vancouver, British Columbia, Canada) administration and pulsed light delivery. The prostate gland of 11 dogs were infused with QLT0074 via the prostatovesical arteries (2 mg drug per artery bilaterally) under fluoroscopic guidance. Immediately following infusion the prostate was surgically exposed and 7 optical fibers with 1.5 cm cylindrical diffusers in after loading sheaths were inserted into the prostate through a template. Light was delivered sequentially to the optic fibers via a computer driven switch system. One dog was sacrificed 6 days after photodynamic therapy to assess acute tissue effects. The other 10 dogs were monitored for clinical tolerance and urinary function, and sacrificed at between 3 and 11 months. Prostate specimens were examined microscopically to evaluate long-term tissue reactions. Comprehensive destruction of the prostate was noted in the acute dog. Except for urinary retention and mild hematuria no other perioperative complications were observed in the chronic dogs. Urodynamic examination did not reveal deleterious bladder and urethral function. Average prostate volume decreased 71% at 3 months and 56% after 6 months (p=0.007 and 0.014, respectively). Microscopic evaluation revealed prostate glandular epithelial atrophy, stromal fibrosis and mononuclear cell infiltration. Interstitial photodynamic therapy using intra-arterial QLT0074 and pulsed light delivery is safe and feasible for comprehensive destruction of the canine prostate. Clinical trials are required to confirm it for managing prostate diseases.

Photodynamic Therapy for Urological Malignancies: Past to Current Approaches

Modern PDT for urological tumors is a potentially selective approach in which in situ photosensitization by a nontoxic drug, locally activated by light, generates cytotoxic reactive oxygen species, causing cell death. While urological clinical experience with PDT is largely limited to treatment for superficial bladder cancer, the advent of novel photosensitizers and technologies for treatment planning, light delivery and dosimetry, PDT for prostate and other urological cancers appears increasingly realistic. We reviewed the current literature on PDT for urological tumors, in addition to recent emerging data from our laboratory and elsewhere. Remarkable progress has been made in the field of photochemistry and photobiology. Together with improved optical delivery and imaging systems PDT holds promise as an alternative, minimally invasive and potentially curative treatment for localized solid tumors as well as for palliative treatment for isolated, clinically problematic metastases. Current experience with photodynamic therapy using contemporary photosensitizing agents and light sources is mainly restricted to in vivo experimental models and early phase clinical trails. However, ongoing preclinical work and clinical trials indicate that safer and effective PDT treatments in uro-oncology are imminent.

Separation of porphyrin-based photosensitizer isomers by laser-induced fluorescence capillary electrophoresis

Methods for the separation of photosensitizer isomers, such as benzoporphyrin derivative monoacid, benzoporphyrin ethyl monoacid, 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a, diethyleneglycol diester benzoporphyrin derivative, tin ethyl etiopurpurin, and phthalocyanine tetrasulfonate, have been systematically developed by CE. Detection was accomplished by UV absorption at 214 nm or by LIF with excitation at 442/488 nm and emission at 690 nm. The effects of three major experimental parameters of buffer types, organic solvents, and surfactant additives are described. The optimized separation conditions were determined so as to provide satisfactory separation efficiency and analysis time. The methods are shown to be suitable for the separation and determination of porphyrin and phthalocyanines regioisomers, diastereoisomers, and enantiomers.

Rostaporfin: PhotoPoint SnET2, Purlytin, Sn(IV) etiopurpurin, SnET2, tin ethyl etiopurpurin.

The photosensitiser rostaporfin [Purlytin trade mark, SnET2, tin ethyl etiopurpurin, Sn(IV) etiopurpurin, PhotoPoint SnET2] was developed by Miravant Medical Technologies (USA) for use in the company's PhotoPoint trade mark photodynamic therapy. The therapy relies on low power, non-thermal light produced by a solid-state diode laser, sourced from the device co-developing partner, Iredex Corporation. Mirvant is currently undergoing discussions for potential licensing agreements with leading ophthalmology companies for rostaporfin. In June 2002, Miravant and Bausch & Lomb signed a non-binding letter on intent. The companies are expected to jointly review phase III clinical data concerning rostaporfin. Following the review Bausch & Lomb may negotiate an exclusive worldwide license to develop and commercialise the agent for ophthalmological indications. Previously, in June 1995, Miravant granted Pharmacia & Upjohn (now Pfizer) an exclusive worldwide license for development and marketing of rostaporfin. However, this agreement was terminated in March 2002, at which time Miravant regained the rights to all assets related to rostaporfin. In April 2000, Monsanto merged with Pharmacia & Upjohn to form Pharmacia Corporation. Subsequently, on 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer. Preclinical studies had been underway for other vision-threatening eye diseases, as it also has potential in the treatment of diabetic retinopathy and glaucoma. The US FDA had granted fast-track status to rostaporfin for the treatment of age-related macular degeneration in 1998.

Structural characterization of a degradation product of tin ethyl etiopurpurin (SnET2): Comparison of the long‐range heteronuclear correlations detected using conventional GHMBC and IMPEACH‐MBC in conjunction with submicro NMR probe technology

AbstractDuring the terminal heat sterilization of the lipid emulsion final dose formulation of the photodynamic therapeutic (PDT) agent tin ethyl etiopurpurin (SnET2), a new degradant was observed at very low levels. The degradant, which was prone to photo‐instability, was isolated by preparative chromatography and subsequently characterized by mass spectrometry and NMR methods. Reproducible parent ion clusters were only observable via negative ion APCI methods. Because of the limited isolate sample, NMR characterization was done using 1.7 mm SMIDG (SubMicro Inverse‐Detection Gradient) NMR probe technology in conjunction with the accordion‐optimized IMPEACH‐MBC long‐range heteronuclear shift correlation experiment. The “static” 8 Hz optimization of the GHMBC experiment failed to allow the observation of a number of long‐range correlations that were of critical importance to the determination of the structure of the impurity. In contrast, all of the correlations required to assemble the structure were obtained from an IMPEACH‐MBC experiment optimized for long‐range heteronuclear couplings in the range from 2–10 Hz.

STUDIES OF TIN ETHYL ETIOPURPURIN PHOTODYNAMIC THERAPY OF THE CANINE PROSTATE

Previous studies have demonstrated the technical feasibility of destroying prostate tissue using photodynamic therapy for benign and malignant disease. A series of canine studies was performed to evaluate the systemic uptake and distribution of the photosensitizer tin ethyl etiopurpurin (SnET2) in the prostate and surrounding tissues, and determine the optimal combination of drug dose, light dose and time interval between drug and light administration using transurethral and transperineal interstitial light delivery. Adult male mongrel source dogs received intravenous bolus injections of 0.5 or 1.0 mg./kg. SnET2 in 4 studies. In the first study the concentration of SnET2 in the prostate and surrounding tissue was measured at various time points after dosing. In the second study a tissue dose response relationship of SnET2-PDT was studied after transperineal interstitial light application. The third and fourth studies evaluated the tissue effects of combined transurethral and transperineal interstitial light application on SnET2 sensitized prostates. Substantial amounts of SnET2 were measured in the prostate between 24 and 168 hours after infusion. Drug and light dose dependent prostatic tissue necrosis and volume reduction were documented in the dose response relationship study. The combination of transurethral and transperineal light resulted in the extensive destruction of glandular epithelium with minimal damage to surrounding structures. Average prostate volume decreased 52%. Transperineal interstitial light delivery with multiple diffusers resulted in substantial glandular destruction of the prostate. An average volume reduction of more than 60% was achieved. SnET2-PDT is a viable minimally invasive treatment modality for prostate tissue destruction.

Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.

The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET 2), and meta-tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. © 2000 Cancer Research Campaign

Photodynamic therapy: a new approach to the treatment of choroidal neovascularization secondary to age-related macular degeneration.

Visual loss as a result of choroidal neovascularization secondary to age-related macular degeneration continues to be a major challenge for all ophthalmologists. Photodynamic therapy represents an exciting and novel technique that uses light-activated drugs and nonthermal light to achieve the selective destruction of choroidal neovascularization with minimal effects on the surrounding normal tissues. In Phase I-II clinical trials of photodynamic therapy with both benzoporphyrin derivative and tin ethyl etiopurpurin, closure of choroidal neovascularization was seen 24 hours after the treatment. However, recurrence of choroidal neovascularization can occur 2 to 3 months after treatment. Double-blind, multicenter, randomized Phase III clinical trials with benzoporphyrin derivative and tin ethyl etiopurpurin are currently underway.

Photodynamic Therapy of the Rat Endometrium by Systemic and Topical Administration of Tin Ethyl Etiopurpurin

The objective of this study was to determine the optimal parameters for endometrial destruction by photodynamic therapy (PDT) using tin ethyl etiopurpurin (SnET2) as a photo-sensitizer in the rat model. Different application routes and different time intervals after drug administration were compared when the uterine horn was illuminated with a fixed laser light dose of 375 J/cm2. Then PDT was performed 1.5 h after IV injection of 2 mg/kg SnET2 using decreasing light doses. Destruction of all endometrial glands was observed when the uterine horn was illuminated 1.5 h after IV drug administration. In contrast, weaker PDT effects were observed when light activation was delayed for 24 h following systemic or topical drug application even if the light dose was increased by a factor of 30. Endometrial fluorescence did not prove to be an effective method to predict optimal timing for photodynamic therapy, which was probably due to its binding to serum proteins. For photodynamic treatment of endometrial glands in the rat, IV administration 1.5 h before illumination was most efficient. (J GYNECOL SURG 15:71, 1999)

Photophysical Properties of Tin Ethyl Etiopurpurin I (SnET2) and Tin Octaethylbenzochlorin (SnOEBC) in Solution and Bound to Albumin

The photophysical characteristics of two second-generation PDT photosensitizers, tin ethyl etiopurpurin I (SnET2) and tin octaethylbenzochlorin (SnOEBC), have been measured in homogeneous solution and when bound to bovine serum albumin (BSA). The ground state and triplet state absorption spectra have been characterized, as have triplet lifetimes and quantum yields for intersystem crossing, singlet oxygen formation and photobleaching. In total, these parameters provide a complete set of data that can be used to quantitatively compare the photosensitizing efficiencies of these molecules. The photo-bleaching quantum yield of SnET2 is increased dramatically when it is bound to BSA, thus limiting the production of singlet oxygen at incident fluences above 1 J/cm2. In contrast, the quantum yield of photobleaching of SnOEBC is at least an order of magnitude lower than that of SnET2 under these conditions and does not significantly limit the photosensitization process for typical in vivo or in vitro fluences. This difference is expected to play a significant role in determining the relative photo-sensitizing ability of these compounds in vivo.

Photodynamic Therapy for Corneal Neovascularization

Photodynamic therapy with tin ethyl etiopurpurin (SnET2) was evaluated as a treatment modality for rat corneal neovascularization. Escalating light doses at 664 nm were applied focally to corneal neovascularization in rats 10 minutes following an intravenous injection of SnET2 using a low-power diode laser. Controls consisted of light-only and drug-only treatments. Clinical, angiographic, and histopathologic evaluations were performed on the animals up to 28 days after drug and/or light treatment. A drug and light dose-response was seen in producing neovessel closure. In animals treated with SnET2 and the highest light dose (25 J/cm2), all eyes showed occlusion at every follow-up evaluation up to 28 days. Control eyes demonstrated progressive disease at all time points. Photodynamic therapy appears to be safe and effective for eliciting prolonged (> 28 days) occlusion of corneal neovascularization in the rat model with minimal side effects and good clinical outcomes.

Ocular Vascular Thrombosis Following Tin Ethyl Etiopurpurin (SnET2) Photodynamic Therapy: Time Dependencies

To evaluate the optimal time from the end of photosensitizer injection to the commencement of light application for creating characteristic fundus lesions and the time to vascular occlusion following photodynamic therapy (PDT) with tin ethyl etiopurpurin (SnET2). Following intravenous injection of SnET2 0.5 mg/kg or lipid emulsion alone, the fundus of rabbits was irradiated at different times (5 to 240 minutes) after photosensitizer injection using 664 +/- 7-nm laser light with an irradiance of 354 mW/cm2 and fluence of 20 J/cm2. Ophthalmoscopy and fluorescein angiography were performed 1 day after SnET2 PDT. In separate groups of rabbits, treated areas of the fundus were imaged within 30 minutes following PDT using fluorescein vesicle and microsphere angiography with scanning laser ophthalmoscopy to document time of vascular occlusion. All animals were killed 1 day following treatment and eyes were examined by histopathology. Areas of hypofluorescence (indicating vascular occlusion) were seen when activating laser light was applied 5 to 20 minutes after SnET2 injection. Retinal vessels remained perfused in all cases. The time to vascular occlusion was 70 to 120 and 40 to 90 minutes in nonpigmented and pigmented rabbits, respectively. No safety issues were seen. PDT with SnET2 was effective in occluding the choriocapillaris. Activating light needs to be applied within a specific time frame after photosensitizer injection to achieve vascular occlusion.

Photodynamic therapy in the management of metastatic cutaneous adenocarcinomas: case reports from phase 1/2 studies using tin ethyl etiopurpurin (SnET2)

Photodynamic therapy in the management of metastatic cutaneous adenocarcinomas: case reports from phase 1/2 studies using tin ethyl etiopurpurin (SnET2)

Photophysical Properties of Tin Ethyl Etiopurpurin I (SnET2) and Tin Octaethylbenzochlorin (SnOEBC) in Solution and Bound to Albumin

Abstract— The photophysical characteristics of two second-generation PDT photosensitizers, tin ethyl etiopurpurin I (SnET2) and tin octaethylbenzochlorin (SnOEBC), have been measured in homogeneous solution and when bound to bovine serum albumin (BSA). The ground state and triplet state absorption spectra have been characterized, as have triplet lifetimes and quantum yields for intersys-tem crossing, singlet oxygen formation and photobleaching. In total, these parameters provide a complete set of data that can be used to quantitatively compare the photosensitizing efficiencies of these molecules. The photo-bleaching quantum yield of SnET2 is increased dramatically when it is bound to BSA, thus limiting the production of singlet oxygen at incident fluences above 1 J/cm2. In contrast, the quantum yield of photobleaching of SnOEBC is at least an order of magnitude lower than that of SnET2 under these conditions and does not significantly limit the photosensitization process for typical in vivo or in vitro fluences. This difference is expected to play a significant role in determining the relative photosensitizing ability of these compounds in vivo.

Tin ethyl etiopurpurin—induced photodynamic therapy for the treatment of human immunodeficiency virus—associated kaposi's sarcoma

Current local treatments for cutaneous human immunodeficiency virus—associated Kaposi's sarcoma lesions can be less than ideal. Photodynamic therapy (PDT) consisting of a photoreactive drug and a laser light source has been used to treat a variety of neoplasms. This paper presents the case report of a 36-year-old man with multiple Kaposi's sarcoma lesions. Using the photosensitizer tin ethyl etiopurpurin and red light activation 24 hours postinfusion, we achieved excellent subjective and objective response on follow-up examinations to 20 weeks posttreatment. Photodynamic therapy is an outpatient procedure that is well tolerated and highly effective for the treatment of Kaposi's sarcoma lesions. It offers the distinct benefit of effective destruction of multiple lesions in a single session without severe morbidity. PDT should be considered as the first-line treatment of Kaposi's sarcoma, but it also should undergo large clinical trials to fully assess its capabilities

Photodynamic Therapy of the Ciliary Body With Tin Ethyl Etiopurpurin and Tin Octaethyl Benzochlorin in Pigmented Rabbits

The authors used a pigmented rabbit model to investigate two photosensitizers, tin ethyl etiopurpurin (SnET2) and tin octaethyl benzochlorin (BNZ 203), to determine their potential for creating ciliary body injuries during photodynamic therapy (PDT). The biodistribution of SnET2 (n = 10) and BNZ 203 (n = 9) was studied by fluorescence microscopy using a low light detection system, based on charged-coupled device photography, with digital image processing at 1 and 24 hours after injection. PDT with SnET2 (n = 8; 664 +/- 7-nm light; 75 mW/cm2; 50 or 100 J/cm2; 1-mm spot size) and BNZ 203 (n = 6; 689 nm; 75 mW/cm2; 50 or 100 J/cm2; 1-mm spot size) was performed at 24 hours post-injection. The control subjects for SnET2 (n = 5) and BNZ 203 (n = 3) were given a maximal light dose (100 J/cm2). Both photosensitizers demonstrated an intravascular distribution at 1 hour that shifted to a ciliary body distribution at 24 hours (SnET2 much greater than BNZ 203). In addition, the SnET2 demonstrated suborgan localization to the nonpigmented ciliary body epithelium. Both photosensitizing agents were able to produce selective injury to the rabbit ciliary body (SnET2 much greater than BNZ 203), with evidence of a small component of thermal damage (SnET2 greater than BNZ 203). PDT with SnET2 or BNZ 203 can produce selective injury to the pigmented rabbit ciliary body. The nonpigmented ciliary body epithelium exhibits selective retention of SnET2. This finding warrants further investigation.

1161 - Treatment of gutaneous Kaposi's sarcoma with tin ethyl etiopurpurin (SnET2) photodynamic therapy

1161 - Treatment of gutaneous Kaposi's sarcoma with tin ethyl etiopurpurin (SnET2) photodynamic therapy

Increased photosensitivity in HL60 cells expressing wild-type p53.

Loss of p53 function has been correlated with decreased sensitivity to chemotherapy and radiation therapy in a variety of human tumors. Comparable analysis of p53 status with sensitivity to oxidative stress induced by photodynamic therapy has not been reported. In the current study we examined photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)-based photosensitizer. Total SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation conditions could be adjusted to achieve equivalent cellular PH levels during experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2-mediated photosensitization, as well as to UVC irradiation, when compared to HL60 cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response was observed following purpurin- and porphyrin-induced photosensitization in all cell lines. Results of this study indicate that photosensitivity is increased in HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells.

Photodynamic therapy using SnET2 for basal cell nevus syndrome: a case report

A 26-year-old man with basal cell nevus syndrome presented to the Rocky Mountain Cancer Center (Denver, Colorado) for treatment of several basal cell carcinomas with photodynamic therapy using tin ethyl etiopurpurin (SnET2). The patient was of northern European descent, had type I skin (always burns, never tans), and had a 10-year history of multifocal basal cell carcinomas. The patient had a family history of Gorlin's syndrome (basal cell nevus syndrome); the syndrome had been diagnosed in this patient in 1985. The patient was enrolled in a Phase I/II clinical trial. He was given 1.2 mg/kg (94 mg total) of SnET2 via intravenous infusion; he returned to the clinic the following day for red light application. Thirteen lesions, in 12 treatment fields, were illuminated with light totaling 200 J/cm 2 at a fluence of 150 mW/cm 2. At the 3-month follow-up examination, all tumors were graded as having a complete response by modified AIDS Clinical Trials Guidelines oncologic standards. No evidence of recurrence has been noted during the 6-month follow-up period.