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Biomedical subjects

T Hasan

Publications and source records attributed to T Hasan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Photophysical and photosensitizing properties of benzoporphyrin derivative monoacid ring A (BPD-MA).

The photophysical properties of benzoporphyrin derivative monoacid ring A (BPD-MA), a second-generation photosensitizer currently in phase II clinical trials, were investigated in homogeneous solution. Absorption, fluorescence, triplet-state, singlet oxygen (O2 (1 delta g)) sensitization studies and photobleaching experiments are reported. The ground state of this chlorin-type molecule shows a strong absorbance in the red (lambda approximately 688 nm, epsilon approximately 33,000 M-1 cm-1 in organic solvents). For the singlet excited state the following data were determined in methanol: energy level, Es = 42.1 kcal mol-1, lifetime, tau f = 5.2 ns and fluorescence quantum yield, phi f = 0.05 in air-saturated solution. The triplet state of BPD-MA has a lifetime, tau T > or = 25 microseconds, an energy level, ET = 26.9 kcal mol-1 and the molar absorption coefficient is epsilon T = 26,650 M-1 cm-1 at 720 nm. A dramatic effect of oxygen on the fluorescence (phi f) and intersystem crossing (phi T) quantum yields has been observed. The BPD-MA presents rather high triplet (phi T = 0.68 under N2-saturated conditions) and singlet oxygen (phi delta = 0.78) quantum yields. On the other hand, the presence of oxygen does not significantly modify the photobleaching of this photostable compound, the photodegradation quantum yield (phi Pb) of which was found to be on the order of 5 x 10(-5) in organic solvents.

In Vitro Techniques↗
PubMed1994

[Selective occlusion of subretinal neovascularization with photodynamic therapy].

Conventional photocoagulation of subretinal membranes induces a non-selective thermal necrosis of retinal and choroidal layers with extensive collateral damage. Hence, this modality is of limited value for the treatment of lesions close to or underneath the fovea. Photodynamic therapy uses systemic administration of a primarily non-toxic photosensitizer with localized light activation of the dye by subthermal light intensities. It provides intraluminal vascular occlusion by means of localized endothelial damage. Enhanced selectivity for neovascularization is achieved by the use of carrier molecules with increased receptor density on proliferating endothelial cells, e.g. low-density lipoproteins (LDL). Benzoporphyrin derivative (BPD), currently in phase I clinical trials, was complexed with LDL. BPD-LDL was used for photodynamic occlusion of the choriocapillary layer in the rabbit model. Subretinal photothrombosis and collateral damage to neural retina, retinal pigment epithelium, Bruch's membrane and large choroidal vessels were documented by ophthalmoscopy, angiography and light and electron microscopic histology. Homogenous vascular occlusion without retinal destruction was induced with light doses as low as 10 J/cm2. Selective neovascular occlusion by photodynamic therapy may allow occlusion of subretinal membranes while preserving retinal integrity and visual function.

Animals↗
PubMed1994

[Photodynamic therapy of experimental, intraocular tumors with benzoporphyrin-lipoprotein].

Photodynamic therapy (PDT) with its potential for precise localization and absence of severe side effects such as radiation retinopathy may be particularly appropriate for the treatment of intraocular tumors. Benzoporphyrin (BPD), a potent photosensitizer currently in clinical trial, absorbs light at 692 nm, thus allowing sufficient tissue penetration due to minor light absorption in melanin and hemoglobin. The efficiency and selectivity of BPD are significantly pronounced through preassociation with low-density lipoprotein (LDL), since proliferating cells exhibit an increased metabolism of lipoproteins. As an experimental model Greene's melanomas were implanted either into the iris or choroid of albino rabbits. Irradiation at a radiation energy of 80 for iris and 100 J/cm2 for choroidal tumors 3 h after the i.v. injection of BPD-LDL (2 mg/kg) was administered via a laser arrangement with argon-pumped dye-laser, using the slit-lamp. Angiographies and LM/EM histologies were done immediately, and 1, 3, and 14-21 days post-exposure. All 16 treated tumors demonstrated complete regression with a remaining avascular, fibrotic scar. Immediate vascular occlusion within the tumor was seen angiographically, suggesting a direct vascular mechanism. Histologically, two primary mechanisms could be detected: destruction of neovascular endothelial cells and intracellular tumor cell damage. These results indicate that PDT using BPD-LDL complexes may provide an efficient and selective modality for the management of intraocular neoplasms. The availability of new and potent photosensitizers may also lead to broader clinical applications.

Animals↗
PubMed1993

Pharmacokinetics of a fluorescent drug using laser-induced fluorescence.

Laser-induced fluorescence has been used to measure tissue levels of chloroaluminum sulfonated phthalocyanine in vivo in an implanted hamster cheek pouch carcinoma tumor model. The drug was excited at 610 nm via a pulsed nitrogen laser-pumped dye laser, and fluorescence intensity was monitored at 684 nm for up to 30 days after drug administration. Data were acquired noninvasively with high temporal and spatial resolution using the laser-induced fluorescence apparatus and were analyzed with a multicompartment pharmacokinetic model. In addition, our published data on a C6-BAG glioma rat brain tumor model were analyzed to illustrate the effect of different tumor models on the rates. The rates extracted from the pharmacokinetic model elucidate the mechanisms of drug uptake and retention in the cheek pouch and brain tumor models. The laser-induced fluorescence approach should lead to better drug dosimetry for photochemotherapy and allow quick characterization of the pharmacokinetics of new photosensitizers in tissue.

Animals↗
PubMed1993

Tumor-secreted vascular permeability factor/vascular endothelial growth factor influences photosensitizer uptake.

The role of vascular permeability in the preferential accumulation of photosensitizers in tumor tissue was investigated. Two murine tumors [experimental mammary tumor carcinoma (EMT-6) and methylcholanthrene-induced rhabdomyosarcoma (M1S)] and a human bladder carcinoma (EJ) were grown s.c. on the flank in athymic nude mice and analyzed for in vivo vessel permeability, vascular permeability factor (VPF) secretion, and accumulation of the photosensitizer, chloroaluminum sulfonated phthalocyanine. In vivo tumor vessel permeability and vascular volume were quantitated by measuring Evans blue extravasation and accumulation of a high molecular weight fluoresceinated dextran, respectively. VPF was isolated from serum-free tumor cell conditioned medium using heparin-Sepharose affinity chromatography. Dot and Western blots stained with anti-VPF antiserum positively identified VPF in samples from each tumor. Chloroaluminum sulfonated phthalocyanine pharmacokinetics in tumor-bearing mice were measured using a fiber-based spectrofluorometer. In vivo vessel permeability was found to be greatest in M1S tumors, next in EMT-6 tumors and finally in EJ tumors. Consistent with in vivo data, M1S and EMT-6 tumor cells in culture secrete significantly more VPF than EJ tumor cells. Chloroaluminum sulfonated phthalocyanine accumulation was approximately 2 times greater in M1S and EMT-6 tumors compared to EJ tumors. Our data present evidence that photosensitizer accumulation can be correlated to in vivo tumor vessel permeability and VPF secretion of that tumor. Taken together, the data support the hypothesis that vascular permeability differences among tumors play a significant role in the uptake and retention of photodynamic agents.

Animals↗
PubMed1993

Phototoxicity of lumidoxycycline.

Doxycycline (DOTC) is a photosensitizing drug whose mechanism of phototoxicity is complicated by the large variety of stable photoproducts formed. To assess the role of a DOTC photoproduct, lumidoxycycline (LuDOTC), in the photosensitization mechanism of DOTC, MGH-U1 human bladder carcinoma cells were treated in vitro with either DOTC or LuDOTC, and irradiated with the 351-nm emission of an argon-ion laser. Both DOTC and LuDOTC were phototoxic and caused radiant-exposure-dependent inhibition of cellular incorporation of tritiated thymidine. On an absorbed-photon basis, DOTC was about five times as phototoxic as LuDOTC. Cellular uptake of DOTC was about five times as great as that of LuDOTC. Epifluorescence microscopy showed localization of LuDOTC predominantly within cellular membranes, particularly of mitochondria, as well as a low level of LuDOTC fluorescence diffusely within the cytoplasm. Epifluorescence microscopy of cells labeled with the mitochondrial probe, rhodamine 123, showed mitochondrial fragmentation and altered mitochondrial membrane integrity after LuDOTC photosensitization; these effects depended on radiant exposure and were partially reversible by 24 h after irradiation. For both DOTC and LuDOTC, phototoxicity was increased by irradiation in the presence of deuterium oxide and decreased in the presence of sodium azide, effects consistent with an important mechanistic role for singlet oxygen, O2(1 delta g), in the injury. In solution, LuDOTC and DOTC had similar quantum yields for generation of O2(1 delta g) as measured by time-resolved spectroscopy and by O2(1 delta g) trapping. LuDOTC was photostable in solution, but DOTC underwent significant photodegradation. These data demonstrate that DOTC photo-products such as LuDOTC have significant photobiologic activity and may play an important role in the phototoxicity mechanism of DOTC.

Doxycycline↗
PubMed1993

Allergy to systemic and intralesional corticosteroids.

In this study, allergic reactions to systemic or intralesional corticosteroids were characterized, and skin tests utilized in the diagnosis of corticosteroid allergy. Five patients who had developed a rash when treated with systemic or intralesional hydrocortisone, methylprednisolone, prednisolone or betamethasone, were challenged with oral or intra-articular corticosteroid preparations, and skin tested. Upon provocation the patients reacted with diffuse erythema principally on the trunk or on the face. The erythema appeared within a period ranging from a few hours to 24 h and faded in 1-3 days. On patch testing, one patient reacted to prednisolone and methylprednisolone, which induced a positive response upon provocation, and two patients were positive to Pivalone. Patients who were sensitive to hydrocortisone or methylprednisolone, as judged by anamnestic data and provocations, reacted to these corticosteroids in the intradermal tests. Allergy to betamethasone could not be verified by intradermal or patch tests. A combination of intradermal and patch tests is recommended when allergy to systemic or intralesional corticosteroids is suspected. If these skin tests remain negative, provocation is the method of choice.

Administration, Oral↗
PubMed1993

p53 expression and clinical outcome in prostate cancer.

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.

Aged↗
PubMed1993

Chloroaluminum sulfonated phthalocyanine partitioning in normal and intimal hyperplastic artery in the rat. Implications for photodynamic therapy.

Photodynamic therapy, the light activation of photosensitizers into cytotoxic mediators, has been a successful treatment for experimental intimal hyperplasia (IH). To understand the basis of the photosensitizer chloroaluminum sulfonated phthalocyanine (CASPc)-mediated photoinhibition of intimal hyperplasia in the rat common carotid artery model, we studied photosensitizer partitioning in hyperplastic as compared to normal arterial tissue. Serum clearance of CASPc is exponential with, a half-life of 300 minutes. Laser-induced fluorescence and spectrofluorimetric analyses of artery tissue demonstrated an approximately 60% lower uptake and retention of CASPc by normal arterial tissue as compared to arteries with IH; the differences become more pronounced at 24 h. Fluorescent microscopy of arterial tissue demonstrated increased uptake of the CASPc by the artery with IH. However, by 24 h it is primarily the IH tissue that has retained the CASPc, with clearance of the dye from the media of normal or hyperplastic arteries. These data demonstrate that IH, like neoplastic tissue, has an increased accumulation of CASPc compared to normal artery. The preferential partitioning into hyperplastic tissue has implications for therapeutic targeting of this cellular population with photodynamic therapy.

Animals↗
PubMed1992

Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs.

Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer. The goal of this study was to evaluate the effect of PDT using topical ALA on normal guinea pig (g.p.) skin and g.p. skin in which the stratum corneum was removed by being tape-stripped (TS). Evaluation consisted of gross examination, PpIX fluorescence detection, reflectance spectroscopy, and histology. There was no effect from the application of light or ALA alone. Normal non-TS g.p. skin treated with ALA and light was unaffected unless high light and ALA doses were used. Skin from which the stratum corneum was removed was highly sensitive to treatment with ALA and light: 24 h after treatment, the epidermis showed full thickness necrosis, followed by complete repair within 7 d. Time-dependent fluorescence excitation and emission spectra were determined to characterize the chromophore and to demonstrate a build-up of the porphyrin in the skin. These data support the view that PDT with topical ALA is a promising approach for the treatment of epidermal cutaneous disorders.

Administration, Topical↗
PubMed1992

Role of neovasculature and vascular permeability on the tumor retention of photodynamic agents.

A variety of photodynamic sensitizers (chloroaluminum sulfonated phthalocyanine, tetraphenyl porphine sulfonate, mono-L-aspartyl chlorin e6, Photofrin, chlorin e6, and Uroporphyrin dihydrochloride I) were characterized by their ability to be retained in EMT-6 tumors growing in BALB/c mice. Two properties uniquely associated with tumors, proliferating neovasculature and vascular permeability, were tested for their relative importance in retaining the photosensitizer. A chick embryo model was used to compare photosensitizer uptake/retention in proliferating and nonproliferating neovasculature with retention in proliferating nonvascular tissue. Our results provide evidence that photosensitizers which are preferentially retained by tumors have a selective affinity for proliferating neovasculature. The chloroaluminum sulfonated phthalocyanine and tetraphenyl porphine sulfonate compounds possess the greatest affinity for proliferating neovasculature relative to nonvascular tissue, while the phthalocyanine has the largest tumor/normal differential in vivo of all the photosensitizers tested. Chlorin e6 and uroporphyrin dihydrochloride I were the only photosensitizers which were not retained in greater amounts by tumor tissues relative to normal tissues. Using a delayed-type hypersensitivity reaction, extended and constant vascular permeability was induced in BALB/c mice. Vascular permeability was quantitated by Evans blue extraction from the delayed-type hypersensitivity sites. Interestingly, leaky vessels alone did not result in photosensitizer retention, as seen with tumors. These data demonstrate that tumor-retained photosensitizers possess a selective affinity for proliferating neovasculature and that vascular permeability alone is not sufficient to retain these sensitizers.

Allantois↗
PubMed1992

Endometrial ablation by means of photodynamic therapy with photofrin II.

OBJECTIVE: Photodynamic therapy is a technique in which tissue is irradiated with light after the use of a photosensitizing drug that produces singlet oxygen, which has a cytotoxic effect. The feasibility of using photodynamic therapy with photofrin II for endometrial ablation was studied. STUDY DESIGN: Fifty-eight rabbits were studied. Preferential uptake of photofrin II by endometrial tissue, compared with the myometrium, was established by drug extraction and fluorescence microscopy after administration of photofrin II intravenously. Dosimetry for endometrial ablation was established by administering photofrin II in 1, 2, 5, and 10 mg/kg doses and laser light (630 nm) at radiant exposures of 100 and 200 J/cm2. Histologic examination was performed at 24 hours, 5 days, and 10 days after treatment. There were two control groups. One group received laser light but no photofrin II, and the other received photofrin II without laser light. RESULTS: The concentration of photofrin II was three times higher in the endometrium than in the myometrium at doses of 1 and 2 mg/kg. Fluorescence microscopy of frozen sections of endometrium and myometrium showed a predominantly perivascular fluorescence from photofrin II. A dose of 1 and 2 mg/kg and a flow of 100 J/cm2 was adequate for endometrial ablation in rabbits. At 24 hours after treatment there was extensive hemorrhage and evidence of cell death in the entire endometrium and mild hemorrhage in 10% to 50% of the inner circular layer of the myometrium. At 5 days after treatment necrosis of the entire endometrium and the inner half of the myometrium was seen, but the outer half of the myometrium and the serosa were normal. There were no cases of uterine perforation. Similar results were seen at 10 days after treatment, except for the additional presence of inflammatory cells. Neither control group (drug without light, light without drug) showed any injury to the endometrium at 24 hours. CONCLUSION: We conclude that endometrial ablation can be effectively achieved in rabbits by means of photodynamic therapy with photofrin II without significant complications.

Animals↗
PubMed1992

Comparison of intravenous and intravesical administration of chloro-aluminum sulfonated phthalocyanine for photodynamic treatment in a rat bladder cancer model.

Photodynamic therapy is an experimental treatment of superficial bladder tumors. Photofrin, a mixture of porphyrins, is the only photosensitizer in clinical use in the U.S.A. and its major side effect is prolonged cutaneous phototoxicity. In order to circumvent this problem of phototoxicity, new photosensitizers are being examined. Cutaneous phototoxicity may also be minimized by local administration of photosensitizer. Therefore, in this study, we investigated the photosensitizer chloro-aluminum sulfonated phthalocyanine (CASPc) in vivo in a rat bladder carcinoma model, and compared two different routes of CASPc administration. AY-27 rat bladder carcinoma cells were transplanted into rat bladders. Eight days after tumor transplantation the biodistribution of CASPc in bladder, skin, muscle and bladder tumor was determined by fluorescence measurements after dye extraction. Photosensitizer administered by intravenous injection and intravesical instillation, were compared. The concentration of CASPc in bladder and bladder tumor after intravenous injection and intravesical instillation was similar. The ratio of dye uptake between tumor and normal bladder after either administration was approximately two. Although no systemic absorption of the photosensitizer was observed after intravesical instillation, there was no reduction in tumor uptake or in the ratio between tumor to normal surrounding tissue. Therefore, no systemic side effects of skin phototoxicity are expected upon intravesical instillation. The microscopic biodistribution of CASPc after intravenous injection and intravesical instillation was also compared. After intravenous injection, the photosensitizer was distributed within the whole tumor with increased fluorescence around the microvasculature. In the normal bladder wall, weak fluorescence was seen in the area of the vasculature in the submucosa and the muscularis. After intravesical instillation, strong fluorescence was detected only at the tumor surface and in normal urothelium; no fluorescence was found in other areas of the tumor or in submucosa or muscularis. A comparison of the photodynamic treatment of model bladder tumors showed that tumor destruction after either method was similar but that there were less side effects to normal bladder wall after intravesical instillation of the CASPc. Intravesical administration of photosensitizers may, therefore, be a viable alternative to intravenous injection with potential for reduced systemic and normal tissue toxicity.

Administration, Intravesical↗
PubMed1992

A self-administered patient questionnaire in the assessment of symptoms before and after prostatectomy.

A self-administered patient questionnaire was developed to assess the severity of key symptoms before and after transurethral prostatectomy (TURP). This questionnaire was validated by comparison with a standard assessment performed by the doctor. Complete data were obtained on 39 men studied before and 3 months after prostatectomy. Close associations were found between the scores resulting from the assessments performed by the patient and those carried out by the doctor. These associations were found for individual scores and for aggregate scores for obstructive and irritative symptoms before and after operation. Symptom scores after operation were significantly related to the patients' overall assessment of whether the operation had been a success--a low score being associated with a satisfactory outcome. It is suggested that self-administered symptom questionnaires can give a reliable picture of the outcome of prostatectomy and might be useful in developing audit systems.

Humans↗
PubMed1992

Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia.

BACKGROUND: Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death. METHODS AND RESULTS: The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n = 6) or saline (n = 3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 10(3) seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean +/- SD decrease of IH in the PDT-irradiated segments of the arteries (0.06 +/- 0.05 mm2) versus the laser-only control ones (0.17 +/- 0.07 mm2) (t test, p less than 0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT-mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations. CONCLUSIONS: These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long-term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.

Aluminum↗
PubMed1992

[Selective occlusion of ocular neovascularization by photodynamic therapy].

Photodynamic therapy (PDT) has successfully been used to induce vascular occlusion via endothelial damage and subsequent thrombosis. To increase the selective of this method for neovascularizations, characteristics in the ultrastructure of the proliferative vessel wall allow physiological vessels to be spared and predominantly neovascularizations to be occluded: (a) Due to the disturbance of the blood-retina barrier, free dye molecules accumulate within the vascular wall. Using a dye with prolonged retention, such as phthalocyanine (CASPc), it is possible to thrombose neovascularizations 24 h post injection while leaving the physiological vasculature of the anterior segment of the rabbit eye unaffected. (b) Proliferating endothelial cells express high numbers of low-density lipoprotein (LDL) receptors. Chlorin e6 (Ce6), a potent photosensitizer, is covalently bound to LDL. Intravascularly, ce6-LDL complexes selectively label neovascular walls. Since ce6-LDL is incorporated intracellular into enzymatically active lysosomes, photothrombosis is effectively achieved at low drug and light doses in vivo. In addition, the induced damage is spatially confined to the inner vascular lining. We conclude that carrier-mediated PDT may offer a new and sensitive approach for selective treatment of intraocular neovascularizations.

Animals↗
PubMed1991

Photoimmunotherapy of human ovarian carcinoma cells ex vivo.

Photodynamic therapy is a relatively new and potentially selective experimental approach to the treatment of malignant neoplasms. Its inherent dual selectivity is reinforced by the use of photosensitizer-monoclonal antibody conjugates. The goal of this study was to evaluate the phototoxicity and selectivity of an immunoconjugate (IC) synthesized from a chlorin derivative chlorin e6-monoethylenediamine monoamide (CMA) as the photosensitizer and an anti-ovarian carcinoma monoclonal antibody OC125. Binding efficiency and specificity of the IC were determined by enzyme-linked immunosorbent assay, and specific covalent linkage of the monoclonal antibody to the photosensitizer was demonstrated by fluorescence and electrophoresis. Phototoxicity was tested against ascites or pleural fluid cells from 15 patients with ovarian and nonovarian cancers. Tumor cells from the fluid were treated with the IC at 3 microM equivalent CMA concentration and irradiated at 654 nm (lambda max CMA in IC) at 25 J/cm2 from an argon ion-pumped dye laser. Phototoxic efficacy was assayed by [3H]thymidine incorporation. Ovarian cancer cells exhibited high cytotoxicity with [3H]thymidine incorporation of 2.4 +/- 2.2%, while nonovarian cancer cells under identical conditions exhibited none to reduced cytotoxicity with [3H]thymidine incorporation of 70 +/- 54%. Using a Wilcoxon test, there was a statistically significant difference between these two groups (P less than 0.001). Dose-response curves revealed reciprocity in photosensitizer concentration and fluence. These results demonstrate that photoimmunoconjugates retain significant antigen binding specificity and affinity, are effective in the selective photochemical eradication of target cells, and merit further evaluation as photochemotherapeutic agents.

Antibodies, Monoclonal↗