Characteristics of in vivo radiotherapy dosimetry.

The recent discussion and debate about the use of in vivo dosimetry as a routine component of the radiotherapy treatment process has not included the limitations introduced by the physical characteristics of the detectors. Although a robust calibration procedure will ensure acceptable uncertainties in the measurements of tumour dose, further work is required to confirm the accuracy of critical organ measurements with a diode or a thermoluminescent dosemeter outside the main field owing to limitations caused by a non-uniform X-ray energy response of the detector, differences between the X-ray energy spectrum inside and outside the main field, and contaminating electrons.

Measurement of the internal dose to families of outpatients treated with 131I for hyperthyroidism.

OBJECTIVE: The aim of this study was to measure the internal dose received by family members from ingestion of radioactive contamination after outpatient therapy. MATERIALS AND METHODS: Advice was given to minimise transfer of radioiodine. Home visits were made approximately 2, 7 and 21 days after treatment to measure radioactivity in the thyroids of family members. A decay correction was applied to radioactivity detected assuming ingestion had occurred at the earlier contact time, either the day of treatment or the previous home visit. An effective half-life of 6 or 7 days was used depending on age. Thyroid activity was summed if activity was found at more than one visit in excess of the amount attributable to radioactive decay. Effective dose (ED) was calculated using ICRP72. RESULTS AND DISCUSSION: Fifty-three adults and 92 children, median age 12 (range 4-17) years participated. Median administered activity was 576 (range 329-690) MBq (131)I. Thyroid activity ranged from 0 to 5.4 kBq in the adults with activity detected in 17. Maximum adult ED was 0.4 mSv. Thyroid activity ranged from 0 to 11.8 kBq in the children with activity detected in 26. The two highest values of 5.0 and 11.8 kBq occurred in children aged 5 and 14 years from different families. Eighty-five children had no activity or <1 kBq detected. ED was <0.2 mSv in 86 out of 92 children (93%). Previous published data showed 93% of children received an ED

An update survey of UK in vivo radiotherapy dosimetry practice.

A questionnaire was distributed in 2004 to 59 radiotherapy physics departments in the UK to determine whether in vivo dosimetry practice had changed since a similar survey conducted 10 years earlier. The number of centres carrying out central axis dosimetry had increased slightly from 17 centres in 1994 to 22 centres in 2004, with a diode alone being the most commonly used detector. Twice as many centres (43) carried out critical organ dosimetry compared with those carrying out central axis measurements, and this number had also increased slightly above the 1994 value (38). A diode was used by most centres carrying out central axis dosimetry and by about 50% of centres carrying out critical organ dosimetry. The action level adopted by each centre for central axis measurements varied from >+/-3% to >+/-10% difference between the measured and the prescribed dose, with >+/-5% being the most frequent value. It was concluded that there had been little change in in vivo dosimetry practice during the time between the two surveys, and that guidance on the method and applications for in vivo dosimetry is required before recent recommendations for its widespread adoption for routine use can be satisfied.

Effect of electron contamination of a 6 MV x-ray beam on near surface diode dosimetry.

In critical organ in vivo x-ray dosimetry, the relative contaminating electron contribution to the total dose and total detector response outside the field will be different to the corresponding contributions at the central axis detector calibration position, mainly due to the effects of shielding in the linear accelerator head on the electron and x-ray energy spectrum. To investigate these contributions, the electron energy response of a Scanditronix PFD diode was measured using electrons with mean energies from 0.45 to 14.6 MeV, and the Monte Carlo code MCNP-4C was used to calculate the electron energy spectra on the central axis, and at 1 and 10 cm outside the edge of a 4 x 4, 10 x 10 and a 15 x 15 cm(2) 6 MV x-ray field. The electron contribution to the total dose varied from about 8% on the central axis of the smallest field to about 76% at 10 cm outside the edge of the largest field. The electron contribution to the total diode response varied from about 7-8% on the central axis of all three fields to about 58% at 10 cm outside the edge of the smallest field. The results indicated that a near surface x-ray dose measurement with a diode outside the treatment field has to be interpreted with caution and requires knowledge of the relative electron contribution specific to the measurement position and field size.

A survey of MRI quality assurance programmes.

There are currently no national guidelines on appropriate quality assurance (QA) test frequencies for MRI equipment in clinical use. From a random selection of 45 hospitals in England, who were contacted by phone, 35 hospitals agreed to participate in a survey of MRI QA and were sent a questionnaire requesting information on the range and frequency of QA tests, as well as the staff groups who conduct these tests. Twenty-four completed replies were received, representing a 68% response rate from the distributed questionnaires. Of these, 79% undertook some form of QA, typically conducted by the radiographic staff. Tests were most often undertaken on the head coil, but there was a considerable variation in the frequency and range of tests undertaken at different hospitals. For example, exactly half of the respondents conducted signal to noise ratio (SNR) tests on both head and body coils, but only 13% of centres extended this test to other coils. Results from this survey should inform radiology departments regarding practice at other hospitals and should assist in formulating the frequency and scope of appropriate MRI QA programmes.

The low energy X-ray response of the LiF:Mg:Cu:P thermoluminescent dosemeter: a comparison with LiF:Mg:Ti.

LiF:Mg:Cu:P thermoluminescent dosemeters (TLD) can be used for the same X-ray dosimetry applications as LiF:Mg:Ti, with each type having the disadvantage of a response dependent on energy, particularly at low energies. Measurements were made of the response per unit air kerma of LiF:Mg:Cu:P and LiF:Mg:Ti to nine quasi-monoenergetic X-ray beams with mean energies from 12 keV to 208 keV. Each measurement was normalized to the value produced by 6 MV X-rays. LiF:Mg:Cu:P was found to under-respond to a majority of these radiations whereas LiF:Mg:Ti over-responded to a majority. Their smallest relative measured response was produced by the lowest energy beam, and the maximum measured relative response of 1.15+/-0.07 and 1.21+/-0.07 for LiF:Mg:Cu:P and LiF:Mg:Ti, respectively, occurred at 33 keV. Energy response coefficients were derived from these measurements to estimate the error introduced by using either type of TLD to measure the dose from an X-ray spectrum different to that used for its absolute response calibration. It was calculated that if the response of either type of TLD was calibrated at 100 kVp, then an error of no more than +/-2% would be introduced into measurements of tube output at potentials of 50-130 kVp. LiF:Mg:Cu:P was found to introduce a larger error (up to 30%) into the measurement of body exit dose than LiF:Mg:Ti at tube potentials of 40-150 kVp, if its absolute response was calibrated using the corresponding body entrance beam. The method should allow this type of error to be estimated in other dosimetry applications for either type of TLD.

Patient radiation doses during invasive cardiac procedures categorised by clinical code.

Patient radiation doses delivered during invasive fluoroscopic cardiology procedures at the University Hospital of North Staffordshire during a 3 year period from November 1999 to August 2002, and comprising 6189 patient records, have been analysed. Cases have been stratified using classification codes from the Office of Population Census and Surveys (OPCS-4 codes), allowing representative doses to be assessed for 34 distinct types of cardiac radiological procedure. In addition, local guidance levels have been derived for the eight most common procedures. This work represents one of the largest and most detailed published studies of patient radiation dose during cardiac procedures, and should assist in meeting the IR(ME)R regulations requirement for establishment of diagnostic reference levels, and in enabling dose optimization of individual exposures.

Near surface photon energy spectra outside a 6 MV field edge.

The purpose of this study was to investigate the difference between a 6 MV linear accelerator x-ray energy spectrum outside the field edge near a phantom surface, and the corresponding spectrum on the central axis. The Monte Carlo code MCNP-4A was used to calculate the spectra on the central axis and at 1, 2, 5 and 10 cm from the edge of a 4 x 4 cm2, 10 x 10 cm2 and 15 x 15 cm2 field. Compared to the spectrum on the central axis, the spectra outside the field edge showed two distinct regions: a broad peak below about 0.5 MeV, and a lower amplitude, less rapidly changing region at higher energies from 0.5 to 6 MeV. The lower energy peak was due to scattered photons, and the higher energy component was due mainly to primary photons transmitted through the jaws of the secondary collimator. The potential impact of these spectral differences on critical organ photon dosimetry was determined by calculating the ratio of the sensitivity of a Scanditronix EDD-5 diode and of a LiF:Mg:Ti thermoluminescent dosimeter (TLD) outside the field edge to their respective sensitivity at the calibration position on the central axis. The lower energy peak combined with the non-uniform energy sensitivity of each detector produced up to a two-thirds overestimate of x-ray dose outside the field by the diode, whereas the response ratio of the TLD was about unity. These results indicated that a similar evaluation was required for profile measurements of a dynamic wedged field and measurements in an intensity modulated beam with either type of detector.

Patient dose optimization in plain radiography based on standard exposure factors.

A computational technique for assessing patient dose in plain radiography is described allowing a large number of examinations to be assessed and enabling dose optimization to be promoted. Entrance surface dose (ESD) was calculated for more than 1500 standard exposure settings in an initial dose assessment. Validation of the technique showed good agreement with thermoluminescent dosimetry and showed broad agreement between the standard exposures and the exposure settings used in practice. The dose assessment was repeated 18 months later using the same techniques for almost 2000 standard exposure settings. In both cases, calculated doses showed good compliance with national diagnostic reference levels where available. Suggested investigation levels were established and set at twice the mean dose for each of 47 examinations. Radiology departments were encouraged to review and optimize doses exceeding these levels. The computed mean ESD in the review study was less than the corresponding value in the initial study in 37 of the 47 examinations. The dose reduction was attributable partly to equipment replacement, but primarily to optimization of exposure settings. The technique employed here provides a valid and cost effective method of complying with statutory requirements for the assessment of representative patient dose and is useful in assisting the ongoing process of dose optimization.

Rapid loss of Oct-4 and pluripotency in cultured rodent blastocysts and derivative cell lines.

The POU transcription factor Oct-4 is essential for the pluripotent character of the mouse inner cell mass (ICM) and derivative embryonic stem (ES) cells. We analyzed the expression of Oct-4 during culture and establishment of cell lines from mouse and rat preimplantation embryos. Oct-4 was rapidly lost in primary outgrowths of the majority of cultured embryos prior to any evidence of morphological differentiation. Oct-4 persisted in only a minority of strain 129 cultures, which can go on to give ES cells. We used transgenic rats in which the dual reporter/selection marker beta-geo is under control of Oct-4 regulatory elements to investigate the effect of direct selection for Oct-4 expressing cells. Ablation of all cells occurred, consistent with complete downregulation of Oct-4. Without selection, in contrast, continuous cultures of morphologically undifferentiated cells could be derived readily from rat blastocysts and ICMs. However, these cells did not express significant Oct-4 and, although capable of differentiating into extraembryonic cell types, appeared incapable of producing fetal germ layer derivatives. Downregulation of Oct-4 appears to be a limiting factor in attempts to derive pluripotent cell lines from preimplantation embryos.

Tetrakis(dimethylamido)vanadium(IV).

The title compound, [V(C(2)H(6)N)(4)], (I), has non-crystallographic D(2d) molecular symmetry and contains an approximately tetrahedrally coordinated V atom with dimethylamido ligands. Each N atom features a nearly trigonal planar geometry. There are two independent molecules of (I) in the asymmetric unit. The results are compared with those previously reported for gas-phase electron-diffraction studies [Haaland, Rypdal, Volden & Andersen (1992). J. Chem. Soc. Dalton Trans. pp. 891-895].

Performance assessment of the Gulmay D3300 kilovoltage X-ray therapy unit.

A performance assessment was made of the Gulmay D3300 kilovoltage (combined superficial and orthovoltage) X-ray therapy unit. Results are presented for the key dosimetric beam parameters required for routine patient treatment. This unit is relatively new to the UK market and displayed similar properties to other existing equipment. Beam half-value layers were different from comparable published data, but were consistent with the actual values of external tube filtration employed. The applicator, system interlocks and dose monitor performance were satisfactory and the tube leakage was below the UK recommended maximum (air kerma rate 300 mGy h(-1) at 5 cm from the tube head). The variation of absorbed dose with stand-off distance from the applicator base followed the inverse-square law for all tested combinations of beam tube potential (kVp) and applicator, and the measured focus-to-surface distances were in acceptable agreement with the nominal values. A significant beam profile asymmetry was seen for field sizes greater than 10 cm at the upper tube potential (kVp) range (maximum ionization quotient 1.08), but this was an inherent property of the X-ray tube. The difficulties of obtaining percentage depth dose measurements are discussed, and it was concluded that the use of published data (appropriately verified) was acceptable. The methodology followed could form the basis of an acceptance and commissioning protocol. To address the relative lack of agreed standards for this type of equipment, performance test tolerances are proposed that are recommended for new installations.

Group 5 imido complexes derived from diamido-pyridine ligands.

Reaction of the vanadium(V) imide [V(NAr)Cl(3)(THF)] (Ar = 2,6-C(6)H(3)(i)()Pr(2)) with the diamino-pyridine derivative MeC(2-C(5)H(4)N)(CH(2)NHSiMe(2)(t)()Bu)(2) (abbreviated as H(2)N'(2)N(py)) gave modest yields of the vanadium(IV) species [V(NAr)(H(3)N'N' 'N(py))Cl(2)] (1 where H(3)N'N' 'N(py) = MeC(2- C(5)H(4)N)(CH(2)NH(2))(CH(2)NHSiMe(2)(t)()Bu) in which the original H(2)N'(2)N(py) has effectively lost SiMe(2)(t)()Bu (as ClSiMe(2)(t)()Bu) and gained an H atom. Better behaved reactions were found between the heavier Group 5 metal complexes [M(NR)Cl(3)(py)(2)] (M = Nb or Ta, R = (t)()Bu or Ar) and the dilithium salt Li(2)[N(2)N(py)] (where H(2)N(2)N(py) = MeC(2-C(5)H(4)N)(CH(2)NHSiMe(3))(2)), and these yielded the six-coordinate M(V) complexes [M(NR)Cl(N(2)N(py))(py)] (M = Nb, R = (t)()Bu 2; M = Ta, R = (t)()Bu 3 or Ar 4). The compounds 2-4 are fluxional in solution and undergo dynamic exchange processes via the corresponding five-coordinate homologues [M(NR)Cl(N(2)N(py))]. Activation parameters are reported for the complexes 2 and 3. In the case of 2, high vacuum tube sublimation afforded modest quantities of [Nb(N(t)()Bu)Cl(N(2)N(py))] (5). The X-ray crystal structures of the four compounds 1, 2, 3, and 4 are reported.

Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei.

Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source of many different cell types for cell-based gene and tissue therapies [1-3]. Nevertheless, if the full potential of cell lines derived from donor embryos is to be realised, the problem of donor-recipient tissue matching needs to be overcome. One approach, which avoids the problem of transplant rejection, would be to establish stem cell lines from the patient's own cells through therapeutic cloning [3,4]. Recent studies have shown that it is possible to transfer the nucleus from an adult somatic cell to an unfertilised oocyte that is devoid of maternal chromosomes, and achieve embryonic development under the control of the transferred nucleus [5-7]. Stem cells isolated from such a cloned embryo would be genetically identical to the patient and pose no risk of immune rejection. Here, we report the isolation of pluripotent murine stem cells from reprogrammed adult somatic cell nuclei. Embryos were generated by direct injection of mechanically isolated cumulus cell nuclei into mature oocytes. Embryonic stem (ES) cells isolated from cumulus-cell-derived blastocysts displayed the characteristic morphology and marker expression of conventional ES cells and underwent extensive differentiation into all three embryonic germ layers (endoderm, mesoderm and ectoderm) in tumours and in chimaeric foetuses and pups. The ES cells were also shown to differentiate readily into neurons and muscle in culture. This study shows that pluripotent stem cells can be derived from nuclei of terminally differentiated adult somatic cells and offers a model system for the development of therapies that rely on autologous, human pluripotent stem cells.

Macrocycle-supported titanium complexes with chelating imido ligands: analogues of ansa-metallocenes.

Reactions of 1,4-dimethyl-1,4,7-triazacyclononane (L1a) and 1,4-diisopropyl-1,4,7-triazacyclononane (L1b) to form 1-aminopropyl-4,7-di-R-1,4,7-triazacyclononane [R = Me (H2L3a) or Pri (H2L3b)] and 1-(2-aminobenzyl)-4,7-di-R-1,4,7-triazacyclononane [R = Me (H2L5a) or Pri (H2L5b)] are reported. Reaction of H2L3a and H2L5a with [Ti(NMe2)2Cl2] gives the ansa-linked macrocycle-imido complexes [Ti(kappa 4-L3a)Cl2] (5a) and [Ti(kappa 4-L5a)Cl2] (6a), respectively, and NHMe2. Reaction of H2L3a with [Ti(NBut)Cl2(py)3] gives [Ti(NBut)(kappa 3-H2L3a)Cl2] (7), which possesses a pendant alkylamine group that does not undergo amine/tert-butylimido group exchange to give 5a and ButNH2. However, reaction of H2L3b and H2L5b with [Ti(NBut)Cl2(py)3] does give amine/tert-butylimido group exchange to form [Ti(kappa 4-L3b)Cl2] (5b), [Ti(kappa 4-L5b)Cl2] (8b), and ButNH2. The compounds 5a,b and 6a,b are isolobal analogues of group 4 ansa-metallocene complexes and relatives of titanium cyclopentadienyl-amido constrained geometry olefin polymerization catalysts. Reaction of 5b with AgOTf affords [Ti(kappa 4-L3b)(OTf)Cl] (8) as the major product, the crystal structure of which has been determined. Alkylation of 6b by RLi gives the dialkyl derivatives [Ti(kappa 4-L5b)(R)2] [R = Me (9) or CH2SiMe3 (10)]. The ethylene polymerization capability of the compounds 5a,b, 6a,b, and 10 in the presence of methylaluminoxane has been determined and compared to that of [Ti(NBut)(kappa 3-L1a,b)Cl2] (11a,b); in all instances, low yields of high-molecular-weight polymer are obtained.