Dosimetric feasibility study for an extracorporeal BNCT application on liver metastases at the TRIGA Mainz.

This study investigates the dosimetric feasibility of Boron Neutron Capture Therapy (BNCT) of explanted livers in the thermal column of the research reactor in Mainz. The Monte Carlo code MCNP5 is used to calculate the biologically weighted dose for different ratios of the (10)B-concentration in tumour to normal liver tissue. The simulation results show that dosimetric goals are only partially met. To guarantee effective BNCT treatment the organ has to be better shielded from all gamma radiation.

Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells.

Irradiation facility at the TRIGA Mainz for treatment of liver metastases.

The TRIGA Mark II reactor at the University of Mainz provides ideal conditions for duplicating BNCT treatment as performed in Pavia, Italy, in 2001 and 2003 [Pinelli, T., Zonta, A., Altieri, S., Barni, S., Braghieri, A., Pedroni, P., Bruschi, P., Chiari, P., Ferrari, C., Fossati, F., Nano, R., Ngnitejeu Tata, S., Prati, U., Ricevuti, G., Roveda, L., Zonta, C., 2002. TAOrMINA: from the first idea to the application to the human liver. In: Sauerwein et al. (Eds.), Research and Development in Neutron Capture Therapy. Proceedings of the 10th International Congress on Neutron Capture Therapy, Monduzzi editore, Bologna, pp. 1065-1072]. In order to determine the optimal parameters for the planned therapy and therefore for the design of the thermal column, calculations were conducted using the MCNP-code and the transport code ATTILA. The results of the parameter study as well as a possible configuration for the irradiation of the liver are presented.

Determination of the irradiation field at the research reactor TRIGA Mainz for BNCT.

For the application of the BNCT for the excorporal treatment of organs at the TRIGA Mainz, the basic characteristics of the radiation field in the thermal column as beam geometry, neutron and gamma ray energies, angular distributions, neutron flux, as well as absorbed gamma and neutron doses must be determined in a reproducible way. To determine the mixed irradiation field thermoluminescence detectors (TLD) made of CaF(2):Tm with a newly developed energy-compensation filter system and LiF:Mg,Ti materials with different (6)Li concentrations and different thicknesses as well as thin gold foils were used.

Flow and pressure during liver preservation under ex situ and in situ perfusion with University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution.

Effective preservation of liver grafts is the first essential step for successful liver transplantation. Insufficient perfusion leads to ischemic-type biliary lesions after transplantation. Perfusion of the graft can be performed either in situ or ex situ, with gravity flow or pressure-controlled. Mainly University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are used widespread in clinical liver transplantation. Due to a persistent lack of data, we performed this systematic investigation of in situ and ex situ perfusion of liver grafts with HTK (low-viscous) and UW (high-viscous) solutions at different pressure steps on the perfusion solution (gravity flow, 50, 100, 150, and 200 mm Hg). End points were perfusion flow and pressure in the hepatic artery. A pig model was used with n = 8 pigs randomized to each (HTK and UW) group. In situ perfusion was ineffective for both solutions at any pressure on the perfusate bag. Ex situ perfusion showed significantly improved flow and pressure in the hepatic artery and, therefore, was highly effective. No major differences between HTK and UW solutions could be detected. Therefore, an additional ex situ perfusion of the hepatic artery should be mandatory in every liver procurement.

Frequency of and interaction between polymorphisms in the beta3-adrenergic receptor and in uncoupling proteins 1 and 2 and obesity in Germans.

OBJECTIVE: To determine the role of polymorphisms in the genes for beta3-adrenergic receptor (beta3-AR) and in uncoupling proteins 1 and 2 (UCP-1, UCP-2) in obesity. DESIGN: Association study with three polymorphisms and obesity. SUBJECTS: Two hundred and thirty-six morbidly obese patients who underwent gastric banding surgery, 381 patients from the medical clinic and 198 healthy blood donors. MEASUREMENTS: The frequencies of the W64R in beta3-AR, the 3826A-->G in UCP-1 and the 45bp insertion in the 3 untranslated region of exon 8 in UCP-2 polymorphisms were determined. RESULTS: There were no significant differences in the frequencies of the beta3-AR and UCP-1 polymorphisms between obese (body mass index, BMI > 30 kg/m2) and lean subjects. Lean, but not obese, carriers of the R allele of beta3-AR had a significantly higher BMI. The mean age of obese subjects (excluding diabetics) who were carriers of the G allele of the UCP-1 polymorphism, 36y, was significantly younger than wild-type, 40y (P= 0.007). This effect was not seen in lean subjects. The effect of the G allele on the mean age of obese subjects was more apparent in subjects who were also carriers of the R allele of the beta3-AR polymorphism. The frequency of the ins allele of UCP-2 was significantly higher in obese subjects, 0.31, than in lean, 0.24 (P= 0.002) and carriers of the ins allele had a significantly higher BMI, 38 vs 35 (P= 0.005). There was no association between any of the polymorphisms and type II diabetes. CONCLUSION: In a German population, there was no association between the W64R in beta3-AR or the 3826A-->G in UCP-1 polymorphisms and obesity. However, they act synergistically to accelerate the development of obesity. The 45bp insertion in the 3 untranslated region of exon 8 in UCP-2 polymorphism is associated with obesity.