Treatment of a maxillary fibrosarcoma in an adult alpaca.

CASE DESCRIPTION: An approximately 5-year-old sexually intact male alpaca was evaluated because of a right-sided maxillary mass that had recurred after previous surgical debulking. CLINICAL FINDINGS: Clinical, radiographic, and CT examination revealed an approximately 1.5-cm-diameter soft tissue mass associated with expansile osteolysis of the maxillary alveolar bone, beginning at the level of the right maxillary third premolar tooth extending caudally to the level of the rostral roots of the second molar tooth. TREATMENT AND OUTCOME: Right partial maxillectomy was performed, and histologic examination revealed an incompletely excised fibrosarcoma with osseous metaplasia. External beam radiation therapy to the tumor bed was initiated 1 month after surgery. Computerized planning was performed, and a total radiation dose of 48 Gy was prescribed in eleven 4.4-Gy fractions. Follow-up CT evaluations 6 and 58 weeks after radiation therapy was completed revealed no evidence of tumor recurrence. No clinical evidence of tumor recurrence was detected through 110 weeks after radiation therapy. CLINICAL RELEVANCE: The oral fibrosarcoma in the alpaca described here was successfully treated with surgical excision and adjuvant radiation therapy, resulting in excellent quality of life of the treated animal.

Multimodal imaging of tumor response to sorafenib combined with radiation therapy: comparison between diffusion-weighted MRI, choline spectroscopy and 18F-FLT PET imaging.

The purpose of this study was to determine the value of different imaging modalities, that is, magnetic resonance imaging/spectroscopy (MRI/MRS) and positron emission tomography (PET), to assess early tumor response to sorafenib with or without radiotherapy. Diffusion-weighted (DW)-MRI, choline (1)H MRS at 11.7 T, and (18)F-FLT PET imaging were used to image fibrosarcoma (FSaII) tumor-bearing mice over time. The imaging markers were compared with apoptosis cell death and cell proliferation measurements assessed by histology. Anti-proliferative effects of sorafenib were evidenced by (1)H MRS and (18)F-FLT PET after 2 days of treatment with sorafenib, with no additional effect of the combination with radiation therapy, results that are in agreement with Ki67 staining. Apparent diffusion coefficient calculated using DW-MRI was not modified after 2 days of treatment with sorafenib, but showed significant increase 24 h after 2 days of sorafenib treatment combined with consecutive irradiation. The three imaging markers were able to show early tumor response as soon as 24 h after treatment initiation, with choline MRS and (18)F-FLT being sensitive to sorafenib in monotherapy as well as in combined therapy with irradiation, whereas DW-MRI was only sensitive to the combination of sorafenib with radiotherapy.

[Molecular pathology of sarcomas. Update on the research group "Molecular Diagnosis of Sarcomas"]. / Molekularpathologie von Sarkomen. Erste Ergebnisse des Sarkomforschungsverbundes KoSar.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

The possibility of a fully automated procedure for radiosynthesis of fluorine-18-labeled fluoromisonidazole using a simplified single, neutral alumina column purification procedure.

A novel fully automated radiosynthesis procedure for [(18)F]Fluoromisonidazole using a simple alumina cartridge-column for purification instead of conventionally used semi-preparative HPLC was developed. [(18)F]FMISO was prepared via a one-pot, two-step synthesis procedure using a modified nuclear interface synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol (NITTP) with no-carrier added [(18)F]fluoride followed by hydrolysis of the protecting group with 1M HCl. Purification was carried out using a single neutral alumina cartridge-column instead of semi-preparative HPLC. The maximum overall radiochemical yield obtained was 37.49+/-1.68% with 10mg NITTP (n=3, without any decay correction) and the total synthesis time was 40+/-1 min. The radiochemical purity was greater than 95% and the product was devoid of other chemical impurities including residual aluminum and acetonitrile. The biodistribution study in fibrosarcoma tumor model showed maximum uptake in tumor, 2h post injection. Finally, PET/CT imaging studies in normal healthy rabbit, showed clear uptake in the organs involved in the metabolic process of MISO. No bone uptake was observed excluding the presence of free [(18)F]fluoride. The reported method can be easily adapted in any commercial FDG synthesis module.

Preclinical studies of [61Cu]ATSM as a PET radiopharmaceutical for fibrosarcoma imaging.

[61Cu]diacetyl-bis(N4-methylthiosemicarbazone) ([61Cu] ATSM) was prepared using in house-made diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) ligand and [61Cu]CuCl2 produced via the natZn(p, x)61Cu (180 muA proton irradiation, 22 MeV, 3.2 h) and purified by a ion chromatography method. [61Cu]ATSM radiochemical purity was >98 %, as shown by HPLC and RTLC methods. [61Cu]ATSM was administered into normal and tumor bearing rodents for up to 210 minutes, followed by biodistribution and co-incidence imaging studies. Significant tumor/non-tumor accumulation was observed either by animal sacrification or imaging. [61Cu]ATSM is a positron emission tomography (PET) radiotracer for tumor hypoxia imaging.

Fibrosarcoma tras radiodermitis crónica profesional de larga evolución / Sarcoma caused by long-time occupational cronic radiodermitis

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The importance of electric field distribution for effective in vivo electroporation of tissues.

Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.

Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo.

Pattern recognition has been applied to the analysis of in vivo 31P NMR spectra. Using four different classes of tumour and three types of normal tissue, cluster analysis and artificial neural networks were successful in separating and classifying the majority of samples analysed. Although the phosphomonoester and P(i) regions appeared to be the most important spectral features, data representing the entire 31P spectrum were required for best separation of the tumour and tissue classes.

Relative volume-average murine tumor blood flow measurement via deuterium nuclear magnetic resonance spectroscopy.

A deuterium NMR spectroscopic method to determine relative tumor blood flow (TBF) by measuring the increase in tumor HOD concentration after intravenous injection of 100 microliters D2O (0.9% NaCl) is presented. An integration approach analogous to that validated for positron emission tomographic measurement of cerebral blood flow was implemented. Computer simulations indicated that integration from 30 to 120 s minimizes the sensitivity of the uptake integral to the shape of the arterial input function, which cannot be assessed in each mouse, while maintaining both a nearly linear relationship between TBF and the integral and high NMR signal-to-noise. A strong positive linear correlation was observed between the uptake integral and TBF measured by D2O clearance in both untreated tumors (n = 19; P less than 0.001) and tumors after hyperthermia (n = 16; P less than 0.001). This method can measure relative TBF in tumors with heterogeneous blood flow and is ideally suited to concurrent or interleaved measurement of TBF and metabolism via multinuclear NMR spectroscopy.

Phosphorus metabolites and the distribution of cell cycle phase of RIF-1 tumors in response to 14 Gy irradiation.

Simultaneous measurements of DNA cell phase cycle distributions and in vivo 31P NMR spectroscopy were performed on 40 RIF-1 murine tumors irradiated with 14 Gy of X-radiation. Diploid and tetraploid tumor populations were observed. The cells blocked in G2/M phase were measured as a function of the ratios of tetraploid cell number in G2/M phase versus total cell population measured. The G2/M population reached a maximum at 32 h post irradiation, dropping to control values by 72 h, while the ratio of inorganic phosphate to beta-nucleotide triphosphate dropped significantly at 32 h and remained significantly lower than control up to 72 h post irradiation. Measurements of PME, PDE, PCr, and pH showed no significant variations at any time point. No significant change in host cell population could be observed. Since the measured G2/M population never increased to more than 3% of the total cell population, the change observed in the 31P NMR spectra were not simply the result of possible differences in NMR profiles of the different cell phase populations but were more likely due to a change in the metabolic characteristics or environment of a majority of the cells.