Variations in lithium target thickness and proton energy stability for the near-threshold 7Li(p,n)7Be accelerator-based BNCT

The usable range of thickness for the solid lithium target in the accelerator-based neutron production for BNCT via the near-threshold (7)Li(p,n)(7)Be reaction was investigated. While the feasibility of using a (7)Li-target with thickness equal to that which is required to slow down a mono-energetic 1.900 MeV incident proton to the 1.881 MeV threshold of the (7)Li(p,n)(7)Be reaction (i.e., t(min) = 2.33 microm) has already been demonstrated, dosimetric properties of neutron fields from targets greater than t(min) were assessed as thicker targets would last longer and offer more stable neutron production. Additionally, the characteristics of neutron fields generated by (7)Li(p,n)(7)Be for Gaussian incident protons with mean energy of 1.900 MeV were evaluated at a (7)Li-target thickness t(min). The main evaluation index applied in this study was the treatable protocol depth (TPD) which corresponds to the depth in an irradiated medium that satisfies the requirements of the adapted dose protocol. A maximum TPD (TPD(max)) was obtained for each irradiation condition from the relationship between the TPD and the thickness of boron dose enhancer (BDE) used. For a mono-energetic 1.900 MeV proton beam, the deepest TPD(max) of 3.88 cm was attained at the (7)Li-target thickness of t(min) and a polyethylene BDE of 1.10 cm. When the intended TPD for a BNCT clinical treatment is shallower than the deepest TPD(max), the usable (7)Li-target thickness would be between t(min) and an upper limit t(upper) whose value depends on the BDE thickness used. In terms of the effect of stability of the incident proton energy, Gaussian incident proton energies stable to within +/-10 keV of 1.900 MeV were found to be feasible for the neutron production via the near-threshold (7)Li(p,n)(7)Be reaction for BNCT provided that a suitable BDE is used.     

Measurements of low-energy (d,n) reactions for BNCT. Boron Neutron Capture Therapy.

Neutron yields and energy spectra have been measured for various deuteron-induced reactions at low energy. Neutrons of energy > 100 keV emitted in the 9Be(d,n)10B, 12C(d,n)13N, and 13C(d,n)14N reactions at Ed= 1.5 MeV were detected at five angles by means of liquid scintillator detectors. While low-energy neutrons were observed in all studied reactions, only 13C(d,n)14N is characterized by a relatively large yield with spectral features potentially interesting for an accelerator-based neutron source for BNCT.     

Absolute dosimetry in a d(14 MeV) + Be fast neutron beam

Since 1978, the Universit?tsklinikum in Essen operates a d(14 MeV) + Be fast neutron beam for patient treatment. Dosimetric studies were performed in a rectangular 40 x 40 mm2 neutron/photon field using a transportable water calorimeter, which had been developed at the Physikalisch-Technische Bundesanstalt. The water calorimeter allowed small dosimeters to be directly calibrated in units of absorbed dose-to-water in a cylindrical phantom of 50 mm in diameter. Also, the twin detector method was applied in order to determine the photon and the neutron dose separately. By making use of a calibrated ionization chamber, the absorbed dose-to-water calibration in the cylindrical water phantom was transferred to a water phantom, a cube 300 mm on a side. Experiments and Monte Carlo calculations covering the neutron producing target, the collimator and the influence of the water calorimeter on the spectral neutron fluence at the measurement position allow the relative uncertainty of the absorbed dose-to-water determination to be reduced to 2.6% (1 SD). This direct absorbed dose-to-water determination by calorimetry has shown that the treatment planning system underestimates the physical dose to tissue by 9%. For clinical purposes, the statement of the prescribed dose had to be increased by 9% in order that the absolute absorbed dose remains constant and that the same biological endpoints are reached.     

Study of moderator thickness for an accelerator-based neutron irradiation facility for boron neutron capture therapy using the 7Li(p,n) reaction near threshold

Accelerator neutron sources for epithermal neutron capture therapy utilizing the 7Li(p,n) nuclear reaction will require a moderator even in the threshold range of 1.89 to 1.95 MeV. The corresponding neutron energies allow for a thinner reflector and moderator, with less reduction of the epithermal flux. To estimate the useful neutron flux within the epithermal range (4 eV-40 keV), the optimal thickness of a heavy water moderator was determined using the two-dimensional neutron transport S(N) code DORT. Optimized results are compared with the epithermal fluxes reported for the higher proton energy range, and are found to be inferior. Thus, this study supports the 2.5-3.0 MeV proton energy range for accelerator boron neutron capture therapy.     

Unstable translocation t(14;21) in a man, inherited as a t(13;14) in one of his daughters

The transmission of a Robertsonian translocation was studied in a family after diagnosis of a t rob. (13;14) in a foetus, in the course of a prenatal diagnosis for maternal age. The father was found to be a carrier of a balanced t rob. (14;21) in mosaicism with a normal karyotype. The t rob(14;21) was inherited from the paternal grandfather. A second prenatal diagnosis, 1 year later, revealed a girl with the paternal t rob(14;21). Mitotic and germinal instability of the paternal t rob.(14;21) is discussed, with relation to the long period of drug addiction.     

Irradiation characteristics of BNCT using near-threshold 7Li(p,n)7Be direct neutrons: application to intra-operative BNCT for malignant brain tumours

A calculation method for the dosage of neutrons by near-threshold 7Li(p, n)7Be and gamma rays by 7Li(p, p'gamma)7Li was validated through experiments with variable distance between the Li target and the phantom, focusing on large angular dependence. The production of neutrons and gamma rays in the Li target was calculated by Lee's method and their transport in the phantom was calculated using the MCNP-4B code. The dosage in intra-operative boron neutron capture therapy (BNCT) using near-threshold 7Li(p, n)7Be direct neutrons was evaluated using the validated calculation method. The effectiveness of the usage of the direct neutrons was confirmed from the existence of the region satisfying the requirements of the protocol utilized in intra-operative BNCT for brain tumours in Japan. The boron-dose enhancer (BDE) introduced in this paper to increase the contribution of the 10B(n, alpha)7Li dose in the living body was effective. The void utilized to increase the dose in deep regions was also effective with BDE. For the investigation of 1.900 MeV proton beams, for example, it was found that intraoperative BNCT using near-threshold 7Li(p, n)7Be direct neutrons is feasible.     

Canalicular immunostaining of aminopeptidase N (CD13) as a diagnostic marker for hepatocellular carcinoma

BACKGROUND: Aminopeptidase N (CD13) is expressed in normal and neoplastic liver tissue, where it exhibits a characteristic canalicular pattern (CD13(can)), similar to that seen for CD10 and when antibodies crossreact with biliary glycoprotein I (p-CEA). AIM: To compare the putative diagnostic use of CD13(can) in differentiating between hepatocellular (HCC) and non-hepatocellular carcinomas metastatic to the liver (non-HCC). METHODS: A retrospective study comparing 53 HCC specimens with 32 non-HCC specimens. Immunostaining was performed with HepPar1 and antibodies directed against CD10, CD13, p-CEA, and alpha fetoprotein (AFP). RESULTS: In the HCC group, a canalicular staining pattern was found for CD13, p-CEA, and CD10 in 51, 43, and 33 specimens, respectively. HepPar1 was positive in 29 and AFP in 17 HCC specimens. In the non-HCC group, canalicular immunostaining for CD10 and p-CEA was confined to non-neoplastic liver tissue. One poorly differentiated cholangiocarcinoma showed apical expression of CD13, resembling to some extent CD13(can). Sensitivity and specificity were 96.2% and 97.0%, respectively, for CD13(can), 81.1% and 100% for p-CEA(can), 62.3% and 100%, for CD10(can), 54.7% and 99.9% for HepPar1, and 32.1% and 100% for AFP. CONCLUSIONS: These results show that CD13(can) is more sensitive in differentiating between HCC and non-HCC than CD10(can), p-CEA(can), HepPar1, and AFP.     

A new rapid method for quantification of nitrogen in human serum employing the 14N(p,p' gamma)14N reaction: application to human pregnancy

The total nitrogen concentrations in dried serum from 54 pregnant women and 17 newborn babies were determined by a new application of the 14N(p,p' gamma)14N reaction resonance at 3.9 MeV. The samples were bombarded in a He atmosphere by 4.1 MeV protons from a tandem Van de Graaff accelerator. The mean dry-weight nitrogen concentration in serum sampled during early pregnancy (6-12 weeks; 13.9 g per 100 g +/- 5.4%) was significantly higher than that in serum sampled during late pregnancy (38-42 weeks: 13.0 g per 100 g +/- 3.9%, p less than 0.001) and than that in serum taken from the umbilical cord (13.3 g per 100 g +/- 4.6%, p less than 0.01). The nitrogen levels measured using this rapid nuclear technique, applied for the first time to human serum analysis, agree well with parallel Kjeldahl analyses.     

TPD-based evaluation of near threshold mono-energetic proton energies for the (7)Li(p,n)(7)Be production of neutrons for BNCT

An evaluation of mono-energetic proton energies ranging from 1.885 MeV to 1.920 MeV was carried out to determine the viability of these near threshold energies in producing neutrons for BNCT via the (7)Li(p,n)(7)Be reaction. Neutron fields generated at these proton energies were assessed using the treatable protocol depth (TPD) and the maximum TPD (TPD(max)) as evaluation indices. The heavy charged particle (HCP) dose rate to tumour was likewise applied as a figure of merit in order to account for irradiation time and required proton current. Incident proton energies closer to the reaction threshold generated deeper TPDs compared to higher energy protons when no boron dose enhancers (BDE) were placed in the irradiation field. Introducing a BDE resulted in improved TPDs for high proton energies but their achievable TPD(max) were comparatively lower than that obtained for lower proton energies. In terms of the HCP dose rate to tumour, higher proton energies generated neutron fields that yielded higher dose rates both at TPD(max) and at fixed depths of comparison. This infers that higher currents are required to deliver the prescribed treatment dose to tumours for proton beams with energies closer to the (7)Li(p,n)(7)Be reaction threshold and more achievable proton currents of around 10 mA or less for proton energies from 1.900 MeV and above. The dependence on incident proton energy of the TPD, TPD(max) and the HCP dose rate to tumour with respect to the (10)B concentration in tumour and healthy tissues were also clarified in this study. Increasing the (10)B concentration in tumour while maintaining a constant T/N ratio resulted in deeper TPD(max) where a greater change in TPD(max) was obtained for proton energies closer to the (7)Li(p,n)(7)Be reaction threshold. The HCP dose rates to tumour for all proton energies also went up, with the higher proton energies benefiting more from the increased (10)B concentration.     

Tissue equivalence in clinical neutron dosimetry: comparison of dose distributions in nine tissue substitutes for a d(14)Be neutron beam

Depth dose distributions for a d(14)Be neutron beam, measured separately for total and gamma absorbed dose, are presented for nine tissue substitutes and for two field sizes. These data are used to examine methods to transform depth dose curves from one material to another. Best results are found when the local depths are transformed by constant empirical factors which are independent of depth and field size. As a physical interpretation of the empirical factors, kerma-weighted mean-free-path lengths are calculated for the interaction of the Essen neutron beam with the materials. The ratios of these free path lengths agree with the empirical factors within +/- 10%. However, for clinical dosimetry, a direct comparability of spatial absorbed dose distributions measured in two different phantom materials is only given if their corresponding transformation factor is near unity.     

Evaluation of the characteristics of boron-dose enhancer (BDE) materials for BNCT using near threshold 7Li(p,n)7Be direct neutrons

The characteristics of a number of candidate boron-dose enhancer (BDE) materials for boron neutron capture therapy (BNCT) using near threshold 7Li(p,n)7Be direct neutrons were evaluated based on the treatable protocol depth (TPD), defined in this paper. Simulation calculations were carried out by means of MCNP-4B transport code for candidate BDE materials, namely, (C2H4)n, (C2H3F)n, (C2H2F2)n, (C2HF3)n, (C2D4)n, (C2F4)n, beryllium metal, graphite, D2O and 7LiF. Dose protocols applied were those used for intra-operative BNCT treatment for brain tumour currently used in Japan. The maximum TPD (TPDmax) for each BDE material was found to be between 4 cm and 5 cm in the order of (C2H4)n < (C2H3F)n < (C2H2F2)n < (C2HF3)n < beryllium metal < (C2D4)n < graphite < (C2F4)n < D2O < 7LiF. Based on the small and arbitrary variations in the TPDmax for these materials, an explicit advantage of a candidate BDE material could not be established from the TPDmax alone. The dependence of TPD on BDE thickness was found to be influenced by the type of BDE material. For materials with hydrogen, sharp variations in TPD were observed, while those without hydrogen exhibited more moderate fluctuations in TPD as the BDE thickness was varied. The BDE thickness corresponding to TPDmax (BDE(TPDmax)) was also found to depend on the type of BDE material used. Thicker BDE(TPDmax), obtained mostly for BDE materials without hydrogen, significantly reduced the dose rates within the phantom. The TPDmax, the dependence of TPD on BDE thickness and the BDE (TPDmax) were ascertained as appropriate optimization criteria in choosing suitable BDE materials for BNCT. Among the candidate BDE materials considered in this study. (C2H4)n was judged as the suitable material for near-surface tumours and beryllium metal for deeper tumours based on these optimization criteria and other practical considerations.     

45,XY,-13,-14,-21,+t(13;14),+t(21;21)一例

患儿男,1岁9个月.系第2胎第1产,第1胎人工流产,足月顺产,眼距宽,双手通贯掌,患儿体重9.5 kg,智力低下.父母非近亲结婚,无家族史,生育年龄为母19岁、父26岁.细胞遗传学检查:外周血淋巴细胞培养,G带分析,计数30个分裂相,分析5个,患儿核型为:45,XY,-13,-14,-21,+t(13;14),+t(21;21),父母核型正常.     

Microanalytical techniques for boron analysis using the 10B(n,alpha)7Li reaction

In order to predict the efficacy of boronated compounds for neutron capture therapy (NCT), it is mandatory that the boron concentration in tissues be known. Various techniques for measurement of trace amounts of boron (1-100 ppm) are available, including chemical and physical procedures. Experience has shown that, with the polyhedral boranes and carboranes in particular, the usual colorimetric and spark emission spectroscopic methods are not reliable. Although these compounds may be traced with additional radiolabels, direct physical detection of boron by nondestructive methods is clearly preferable. Boron analysis via detection of the prompt-gamma ray from the 10B(n, alpha)7Li reaction has been shown to be a reliable technique. Two prompt-gamma facilities developed at Brookhaven National Laboratory are described. One, at the 60-MW high flux beam reactor, uses sophisticated beam extraction techniques to enhance thermal neutron intensity and reduce fast neutron and gamma contamination. The other was constructed at Brookhaven's 5-MW medical research reactor and uses conventional shielding and electronics to provide an "on-line" boron analysis facility adjacent to beams designed for NCT, thus satisfying one of the requisites for clinical application of this procedure. Technical restrictions attendant upon the synthesis and testing of boronated biomolecules often require the measurement of trace amounts of boron in extremely small (mg) samples. A track-etching technique capable of detecting ng amounts of boron in mg liquid or cell samples is described. Thus it is possible to measure the boron content in small amounts (mg samples) of antibodies, or boron uptake in cells grown in tissue culture.     

16O(n, p)16N: a fast neutron detector for rapid tissue inhomogeneity correction

We have devised a transit dose technique for fast neutron therapy treatment planning based on the 16O(n, p)16N reaction in recirculating water, and have determined the effect of simulated bone and lung inhomogeneities in phantom. An effective threshold of 10.2 MeV in the 16O(n, p) reaction is exploited to detect transmitted neutrons without the need detector collimation. This system has been demonstrated with 14 MeV (d, T) neutrons and with cyclotron produced p(42) + Be neutrons. 16N decays to the 6.13 MeV excited states of 16O in 7.14 s, allowing for easy identification by NaI(T1) and for rapid recirculation. The transmission of fast neutrons can thus be related to an effective thickness of soft tissue, providing a rapid and direct measure of the effects of inhomogeneities under actual treatment conditions, with the 10 MeV threshold providing a useful degree of insensitivity to multiply scattered neutrons. Equivalent thickness of compact bone and lung relative to water were found to be 1.4 and 0.34 respectively, closely resembling the effective thicknesses for Cobalt-60 gamma rays.     

Chronic myelomonocytic leukemia with t(13;14) in a child

Bone marrow cells from a child with chronic myelomonocytic leukemia showed an acquired, non-Robertsonian translocation between chromosomes 13 and 14, t(13;14)(q12.?2;q32.?3). This rearrangement has not previously been reported in childhood myeloproliferative or myelodysplastic disorders.     

Molecular and cytogenetic characterisation of an unusual case of partial trisomy/partial monosomy 13 mosaicism: 46,XX,r(13)(p11q14)/46,XX,der(13)t(13;13)(q10;q14)

A female infant with multiple malformations and mental retardation was noted to have a rare de novo chromosome abnormality involving mosaicism with two cell lines, one with a ring chromosome 13, and the other with partial trisomy 13 owing to a complex rearrangement. Cytogenetic examination excluded the presence of a t(13q;13q) cell line and showed a cell line with a marker chromosome containing two chromosome 13 long arms joined together after deletion of a part (q11→q14) of one of them. In addition, the absence of a cell line with two normal chromosomes 13 or a cell line with a t(13q;13q) implies that the ring (13) and the marker (13) arose from a single event at the first cleavage division.
The two cell lines were present in different proportions in both peripheral blood lymphocytes and skin fibroblasts. The results of microsatellite characterisation clearly indicate the paternal origin and the absence of recombination, supporting the postzygotic origin of both the ring and the marker chromosome.


Keywords: unusual mosaicism; ring 13; partial trisomy 13; partial monosomy 13     

Multifunctional Ti-(Ca,Zr)-(C,N,O,P) films for load-bearing implants

Films of Ti-Ca-P-C-O-(N), Ti-Ca-C-O-(N) and Ti-Zr-C-O-(N) were deposited by DC magnetron sputtering or ion implantation-assisted magnetron sputtering of composite targets TiC0.5 + 10%Ca10(PO4)6(OH)2, TiC0.5 + 20%(CaO + TiO2) and TiC0.5 + 10%ZrO2 in an Ar atmosphere or reactively in a gaseous mixture of Ar + 14%N2. The microstructure, elemental and phase composition of films were studied by means of X-ray diffraction, transmission electron microscopy, scanning force microscopy, X-ray photoelectron spectroscopy and energy-dispersive X-ray spectroscopy. The films were characterized in terms of their hardness, Young's modulus, elastic recovery, adhesion strength, and friction and wear both in air and under physiological solution. Particular attention was paid to the analysis of deformation and fracture for various film/substrate systems during scratch testing. The biocompatibility of the films was evaluated by both in vitro and in vivo experiments. In vitro studies involved the investigation of adhesion, spreading, and proliferation of MC3T3-E1 osteoblasts and IAR-2 epithelial cells, morphometric analysis, actin cytoskeleton, focal contacts staining, alkaline phosphatase activity and von Kossa staining of osteoblastic culture. Cell culture experiments demonstrated an increase of osteoblastic proliferation on Ca- and P-incorporated films. In vivo studies were fulfilled by subcutaneous implantation of Teflon plates coated with the tested films in mice and analysis of the population of adherent cells on their surfaces. The results obtained show that multicomponent nanostructured Ti-(Ca, Zr)-(C, N, O, P) films possess a combination of high hardness, wear resistance and adhesion strength, reduced Young's modulus, low friction coefficient and high biocompatibility.