Multidetector CT and histological features of benign mesenchymoma of the infratemporal space: a rare case report.

Benign mesenchymoma is a soft tissue neoplasm composed of an admixture of two or more benign mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the infratemporal space in a 14-year-old boy is presented. In this case report we discuss the salient imaging and histopathological features of this rare entity.

Synthesis, dark toxicity and induction of in vitro DNA photodamage by a tetra(4-nido-carboranylphenyl)porphyrin.

The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.

Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors.

The new water-soluble photosensitizer 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]chlorin (T3,4BCPC) has been prepared, characterized and labeled with 99mTc radionuclide. The radiotracer was evaluated for tissue distribution in Wistar rats. Accumulation of administrated activities in the liver, kidney, bladder and large intestine at 4 h post-injection indicated that the labeled ligand was largely eliminated through the renal and partly through the hepatobiliary system. In vivo biodistribution studies of the labeled compound were carried out in rodent and murine tumor models in comparison with other tumor-seeking radiopharmaceuticals such as 99mTc(V)-dimercaptosuccinic acid (DMSA), 201thallous chloride (TlCl) and 99mTc-citrate using a gamma camera computer system. In N-nitrosomethylurea (NMU)-induced rat mammary tumors, the labeled ligand showed a five-fold tumor to muscle (T/M) ratio compared to 99mTc(V)-DMSA (3-fold) and 201TlCl (3-fold). In the case of C(3)H/J virus-induced spontaneous mammary tumors, the differences were not marked. However, in the transplanted rat C(6)-glioma, the T/M ratio of the labeled compound was appreciably higher (four-fold) than that noted with 99mTc(V)-DMSA (two-fold), 201TlCl (three-fold) and 99mTc-citrate (more than three-fold). These findings suggest that the radiolabeled T3,4BCPC may have potential for the detection of cancer. In order to ascertain the efficacy of the compound for photodynamic therapy applications, a preclinical PDT study was carried out in fibrosarcoma-bearing mice after injecting 5.0 mg/kg body weight of the T3,4BCPC. A laser dose of 20 mW for 60 s resulted in 80% destruction of tumors. These data suggest that this molecule could be useful for PDT of cancer. The labeled agent could also be useful in monitoring the progression/regression of tumors before, during, and after chemotherapy, radiation therapy or PDT.

A technetium-99m-labelled cyclam acid porphyrin (CAP) for tumour imaging.

A new water-soluble cyclam acid porphyrin (CAP), 5,10,15,20-tetrakis [4-[4',8',11'-tris(carboxymethyl)-1'-(1',4',8',11'-tetraazacyclotetradecane)amidomethyleneoxy]phenyl] porphyrin has been synthesised, characterised and labelled with 99mTc. In vivo distribution studies were performed in C6-gliomas and N-nitroso-N-methylurea (NMU) induced mammary tumour bearing rats and scintiimages were obtained at 5 h post-administration of the labelled ligand using gamma camera computer system. Tumour to muscle (T/M) ratios were determined and compared with currently available tumour seeking radiopharmaceuticals such as 99mTc(V)-DMSA, 99mTc-Citrate and 201TlCl. In the case of NMU induced mammary tumour rats the ratios were 6.93, 1.97, 5.30 and 3.29; while in the case of C6-gliomas the ratios were 5.58, 2.18, 3.96 and 3.02 for 99mTc-CAP, 99mTc(V)-DMSA, 99mTc-Citrate and 203TlCl, respectively.

Water-soluble 99mTc-labeled dendritic novel porphyrins tumor imaging and diagnosis.

We have synthesized two water soluble dendritic porphyrins, termed DP1 and DP2 and have successfully radiolabeled them with 99mTc. These 99mTc-labeled porphyrins were administered to C6-glioma tumor bearing Wistar rats and scintiimaging and biodistribution studies were carried out. Tumor to muscle ratios of DP1 and DP2 were 8.0 and 9.7, respectively. These molecules may have potential for tumor imaging and diagnosis and may even prove useful as photosensitizers in photodynamic therapy applications.

Technetium-99m-cyclam AK 2123: a novel marker for tumor hypoxia.

Technetium-99m labeled cyclam N-2'-methoxyethyl-2-(3'-nitro-1'-triazole) acetamide (cyclam AK 2123) has been synthesized, radiolabeled and characterized as a hypoxic tumor imaging agent. Radiochemical purity was greater than 95%. Marker biodistribution was measured in normal Wistar strain rats at different time intervals after intra venous (i.v.) administration. In vivo distribution and scintigraphic imaging studies were performed after i.v. injection into mammary tumor-bearing rats using a gamma camera and associated computer. Intratumor partial oxygen pressure (pO2) and oxygen saturation measurements were performed to estimate the oxygenation status of the tumors. Tumor to muscle ratio (T/M) of 99mTc-cyclam AK 2123 was 8.5 which was compared with other tumor seeking radiopharmaceuticals, viz. 99mTc-(V) DMSA (3.07), 99mTc-citrate (5.29) and 201T1C1 (3.29). T/M ratios were also evaluated in comparison with radioiodinated iodoazomycin galactopyronoside (125I-IAZG). The ratio obtained was 18 for 99mTc-cyclam AK 2123 and 20 for 125I-IAZG, respectively. The increased concentration of radioactivity in these tumors suggests that this agent could be labelling hypoxic cells and have utility as an imaging agent.

Estrogen receptor beta regulates sexually dimorphic neural responses to estradiol.

Estrogen receptors (ERs) mediate many sexual dimorphisms in the neuroendocrine system and in behavior. We examined the consequences of the loss of functional estrogen receptor beta (ERbeta) on two sexually differentiated neural responses to estrogen. In wild type (WT) male mice, but not in females, estradiol (E(2)) treatment decreased estrogen receptor alpha immunoreactive (ERalpha-ir) cell numbers in the arcuate nucleus (ARC), the preoptic area (POA), and the ventromedial nucleus (VMN). These sex differences were reversed in ERbeta knockout (ERbetaKO) mice. Castrated ERbetaKOs did not show any change in ERalpha-ir cell number after E(2) treatment. Yet, E(2) decreased ERalpha-ir cell number in ovariectomized ERbetaKOs. Estradiol treatment increased progesterone receptor immunoreactive (PR-ir) cell number in WT female VMN and POA, but no change was noted in brains of WT castrates. In ERbetaKO mice the opposite relationship was found, E(2) treatment increased PR-ir cell number in male, but not in female, brains. Our results show that ERbeta influences several sexually dimorphic neural responses to estrogen. Moreover the data clearly show that ERbeta can modulate neural expression of ERalpha.

Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes.

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.

Oxidative damage induced by a novel porphyrin on rat brain mitochondria and its possible implications in therapy.

Free radical-induced oxidative damage is involved in several pathological disorders. On the other hand, selective induction of peroxidation in diseased tissue is a promising approach to the treatment of cancer by photodynamic therapy. In this study we have used rat brain mitochondria as a model to evaluate the ability of a new water soluble porphyrin, 5,10,15,20-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP), to induce peroxidative damage during photosensitization. Peroxidation in mitochondria, one of the crucial targets of the photodynamic effect, was assessed from the formation of thiobarbituric acid reactive substances and lipid hydroperoxides. The effect on mitochondrial function was estimated from the loss of a mitochondrial marker enzyme, succinate dehydrogenase (SDH). The photodamage was observed to be time- and concentration-dependent of T4CPP. Inhibition studies suggested involvement of singlet oxygen ((1)O2) and, to a lesser extent, of hydroxyl (OH), peroxyl (ROO(-)) and superoxide radicals (O2(-)) in the photodamage. The addition of γ-linolenic acid (a promoter of lipid peroxidation) to the system led to an enhancement of the T4CPP-induced peroxidative damage. Thus, our study indicated that the combination of γ-linolenic acid and T4CPP could enhance the photodynamic effect and has potential applications in photodynamic therapy.

Photocleavage of plasmid DNA by the prophyrin meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin.

meso-Tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (H2T4CPP) cleaves pBR322 plasmid DNA to single strand breaks in the presence of molecular oxygen and visible light. The above photocleavage was much more efficient in D2O buffer of sodium phosphate (pD = 7.4) than H2O buffer of sodium phosphate (pH = 7.4). In addition this photocleavage of plasmid DNA was inhibited in the presence of sodium azide, lipoic acid, tert-butanol or mannitol suggesting the involvement of 1O2 and.OH in the photocleavage of plasmid DNA. The photocleavage was observed to be more efficient in the presence of H2T4CPP than in the presence of H2CPP [meso-tetrakis (4-carboxy-phenyl)porphyrin]. Our spectral studies using UV-visible, fluorescence and circular dichroism techniques suggest that H2T4CPP binds to DNA while H2CPP does not. Thus, the difference in photocleavage may be caused by the nonbinding of H2CPP and by the binding of H2T4CPP to calf thymus (CT) DNA.