manganese(iii)tetraphenylporphine-sulfonate and Breast-Neoplasms

Nine patients with cutaneous metastases of breast cancer were treated using photodynamic therapy. Meso-tetra-(para-sulphophenyl)-porphin (TPPS4) was applied locally at a dose of 0.15-0.3 mg directly to the lesion. The light source was an argon dye laser emitting light of 630 nm at a fluence rate of 312-680 mW cm-2 and a fluence of 150 J cm-2. No signs of local or systemic side effects or toxicity of the photosensitizer were observed. Treatments were well tolerated with no photosensitivity of the skin. Complete destruction of the tumour was observed in three patients, reduction of the tumour size by more than 50% in two patients, reduction-of the tumour size by less than 50% in two patients and no regression in two patients. The advantages of this method include the high concentration of the photosensitizer in the tumour, the extremely low total dose and the lack of side effects. The disadvantages include the less homogeneous distribution of the photosensitizer in the tumour tissue compared with that obtained by intravenous application.

Topics: Aged; Breast Neoplasms; Contrast Media; Female; Humans; Lasers; Manganese; Mastectomy; Metalloporphyrins; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Skin Neoplasms

Topics: Animals; Breast Neoplasms; Contrast Media; Humans; Magnetic Resonance Imaging; Manganese; Metalloporphyrins; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental

Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.

Topics: Animals; Breast Neoplasms; Contrast Media; Dose-Response Relationship, Drug; Female; Humans; Magnetic Resonance Imaging; Manganese; Metalloporphyrins; Mice; Mice, Nude; Transplantation, Heterologous

Topics: Animals; Breast Neoplasms; Contrast Media; Humans; Injections, Intraperitoneal; Magnetic Resonance Imaging; Manganese; Metalloporphyrins; Mice; Mice, Nude; Porphyrins; Transplantation, Heterologous

MRI has been shown as an adapted non-invasive modality for the detection of tumours in humans. The development of paramagnetic contrast agents could add to the MRI diagnosis. With an experimental model of human breast (MX-1) carcinoma developed in nude mice, two different classes of contrast medium were tested. The first class includes the well-known Gd-DTPA and a new nitroxide compound on going development, representing non specific contrast agents. The specific contrast agents are represented by a metalloporphyrin Mn-TPPS4. Non specific contrast agents can add to the differentiation between well vascularized viable tissue and necrotic areas of tumors. While specific contrast agents may specifically target tumorous tissue.

Topics: Animals; Breast Neoplasms; Contrast Media; Cyclic N-Oxides; Female; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Metalloporphyrins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental; Organ Specificity; Organometallic Compounds; Pentetic Acid; Porphyrins; Time Factors