Effect of delivery system on the pharmacokinetics and tissue distribution of bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC), a photosensitizer for tumor therapy.

Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for photodynamic therapy (PDT). Tissue distributions were studied in tumor-bearing rats as a function of delivery system and time following administration. The tumor model was an N-(4-[5-nitro-2-furyl]-2-thiazolyl) formamide (FANFT)-induced urothelial cell carcinoma transplanted into one hind leg of male Fischer 344 rats; isoBOSINC was delivered to the rats by intravenous injection of 0.

Photodynamic therapy of tumors: effects of hematoporphyrin derivative on normal rat intestine.

Hematoporphyrin derivative (HpD) is a complex mixture of dicarboxylic porphyrins in addition to dimers, oligomers and aggregates of variable sizes. The ability of this mixture (and enriched preparations thereof) to be retained by tumors and to sensitize them to destruction by light has led to worldwide studies of the treatment modality called photodynamic therapy (PDT). Understanding how PDT affects normal tissues surrounding the tumor is of crucial importance.

Pharmacokinetic and tissue distribution studies of the photosensitizer bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in normal and tumor-bearing rats.

Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for photodynamic therapy (PDT). Tissue distributions were studied in normal and in tumor-bearing rats as a function of time following intravenous injection of isoBOSINC as a suspension in 10% Tween 80 in saline. The dose studied was 0.

Photosensitizers for tumor therapy: determination of bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) in rat tissue and serum by high-performance liquid chromatography.

Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a synthetic potential photosensitizer for tumor therapy. A new method, which combines solvent extraction and several purification steps, has been developed to determine its presence in tissues. Separation and quantitation of isoBOSINC is done by high-performance liquid chromatography on a silica column with toluene as a mobile phase and using fluorescence detection (lambda ex = 365 nm, lambda em = 750 nm).

A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT induced urothelial tumors.

Rats engrafted with transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors were treated with purpurin derivatives and red light (greater than 590 nm., 360 joules/cm.2).

Morphological study of the combined effect of purpurin derivatives and light on transplantable rat bladder tumors.

Purpurin derivatives, a group of synthetic photosensitizers, were tested for their photodynamic activity against transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urothelial tumors growing in male Fischer 344 rats. Histological examination of tumors in animals treated with the purpurin derivatives and red light (greater than 590 nm, 360 joules/cm2) revealed tumor cell necrosis 24 h after completion of therapy. Control tumors showed no histological change.

Photodynamic treatment of transplantable bladder tumors in rodents after pretreatment with chloroaluminum tetrasulfophthalocyanine.

Chloroaluminum tetrasulfophthalocyanine (AlPCS) was used as a photosensitizer for the photodynamic treatment of transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors. Two groups of six rats each were injected with AlPCS (three micrograms./gm.

Histological study of the effect of hematoporphyrin derivative photodynamic therapy on the rat jejunum.

Hematoporphyrin derivative photodynamic therapy is evolving as a local treatment for neoplastic disease. The emphasis of previous research has been on the determination of mechanisms of tumoricidal activity and defining the tumoricidal porphyrin component in hematoporphyrin derivative. The effect of hematoporphyrin derivative photodynamic therapy on normal tissue has received little attention.

Jejunal blood flow after exposure to light in rats injected with hematoporphyrin derivative.

Experiments were performed to determine the effect of hematoporphyrin derivative (HPD) photodynamic therapy on blood flow to normal rat intestine. A segment of rat jejunum was exposed to red (greater than 590 nm) light (200 mW/cm2) 24 h after the i.v.

Solid-phase purification and analysis of dicarboxylic porphyrins extracted from cultured tumor cells.

We describe here a sensitive method for the purification and analysis of porphyrins present in hematoporphyrin derivative. Hematoporphyrin derivative is a solution containing a complex mixture of dicarboxylic porphyrins such as hematoporphyrin IX, monohydroxyethyl monovinyl deuteroporphyrin isomers, and protoporphyrin IX in addition to porphyrin aggregates of variable molecular sizes. This mixture is known for its ability to be selectively retained by tumor cells and for its cytotoxicity in the presence of light.

Localization of hematoporphyrin derivative in injured bladder mucosa. An experimental study.

Hematoporphyrin derivative, a fluorescent mixture of porphyrins, has the putative property of being retained in neoplastic tissue after systemic administration. This preferential retention is the basis for the use of this agent as a tumor localizer and tumor photosensitizer. The retention of hematoporphyrin derivative in non-neoplastic but regenerating urothelium has not been reported.

Hematoporphyrin derivative photochemotherapy of experimental bladder tumors.

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative photochemotherapy. A series of experiments was undertaken on the transplantable N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide induced urothelial tumor in Fischer 344 rats to determine a dose response for both hematoporphyrin derivative and light. Tumor blood flow was used as the biologic criteria of response.

Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light.

Following hematoporphyrin derivative (HPD) photochemotherapy, blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thia-zolyl] formamide-induced urothelial tumors was determined by a radioactive microsphere technique using either 103Ru or 141Ce. Two tumors were implanted s.c.

The diagnosis of acute intermittent porphyria. Usefulness and limitations of the erythrocyte uroporphyrinogen I synthase assay.

In acute intermittent porphyria (AIP) the inherited metabolic defect residues in a partial enzyme deficiency at the uroporphyrinogen I synthase (URO-S) step of heme biosynthesis. Assay of this enzyme in erythrocytes is increasingly used for diagnosis of the genetic defect. Erythrocyte URO-S activity was measured by three laboratories in members of 14 AIP kindreds and found helpful for diagnosing the asymptomatic carrier state, since activity of the enzyme was usually distributed bimodally.

Mild beta-thalassemia in black subjects.

In two American black families with beta-thalassemia, globin chain synthesis was investigated in vitro. The resultant alpha/beta and alpha/non-alpha labelling ratios were expressed in terms of both specific activity and total counts. In one family, two brothers with clinical presentations compatible with thalassemia intermedia had apparently each inherited two different beta-thalassemia alleles.