Archive for the ‘Medical Physics UPDATE’ category

Differential radio-sensitivities of human chromosomes 1 and 2 in one donor in interphase- and metaphase-spreads after 60Co gamma-irradiation

July 29th, 2009

Background:
Radiation-induced chromosome aberrations lead to a plethora of detrimental effects at cellular level. Chromosome aberrations provide broad spectrum of information ranging from probability of malignant transformation to assessment of absorbed dose. Studies mapping differences in radiation sensitivities between human chromosomes are seldom undertaken. Consequently, health risk assessment based on radio-sensitivities of individual chromosomes may be erroneous. Our efforts in this article, attempt to demonstrate differences in radio-sensitivities of human chromosome-1 and/or -2, both in interphase and metaphase spreads.
Methods:
Upon blood collection, dosimetry and irradiation were performed. Lymphocytes were isolated after whole-blood irradiation with 60Co ?-rays in the dose range of 0–5 Gy for both interphase, and metaphase aberration studies. Induction of premature chromosome condensation in interphase cells was accomplished using a phosphatase inhibitor, calyculin-A. Metaphase spreads were harvested from short-term peripheral blood lymphocyte cultures following colcemid arrest and using an automated metaphase harvester and spreader. Aberration analysis in both interphase and metaphase spreads were done using FISH.
Results:
In interphase, aberrant cell and aberration frequency involving chromosome 1 and/or 2 increased linearly with radiation dose. In metaphase, aberrations increased in a linear-quadratic manner with dose. Our studies ascertain that chromosome-2 is more radio-sensitive than chromosome-1 in both interphase and metaphase stages, albeit the DNA content of chromosome-2 is lesser than chromosome-1 by almost 10 million base pairs.
Conclusion:
Differences in radio-sensitivities of chromosomes have implications in genetic damage, chromosome organization, and chromosome function. Designing research experiments based on our vital findings may bring benefit to radiation-induced risk assessment, therapeutics and development of chromosome specific biomarkers.

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Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats

May 16th, 2009

Background:
Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas.
Methods:
No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant.
Results:
The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, no-carrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions.
Conclusion:
This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma.

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Influence of increased target dose inhomogeneity on margins for breathing motion compensation in conformal stereotactic body radiotherapy

May 16th, 2009

Background:
Breathing motion should be considered for stereotactic body radiotherapy (SBRT) of lung tumors. Four-dimensional computer tomography (4D-CT) offers detailed information of tumor motion. The aim of this work is to evaluate the influence of inhomogeneous dose distributions in the presence of breathing induced target motion and to calculate margins for motion compensation.
Methods:
Based on 4D-CT examinations, the probability density function of pulmonary tumors was generated for ten patients. The time-accumulated dose to the tumor was calculated using one-dimensional (1D) convolution simulations of a ’static’ dose distribution and target probability density function (PDF). In analogy to stereotactic body radiotherapy (SBRT), different degrees of dose inhomogeneity were allowed in the target volume: minimum doses of 100% were prescribed to the edge of the target and maximum doses varied between 102% (P102) and 150% (P150). The dose loss due to breathing motion was quantified and margins were added until this loss was completely compensated.
Results:
With the time-weighted mean tumor position as the isocentre, a close correlation with a quadratic relationship between the standard deviation of the PDF and the margin size was observed. Increased dose inhomogeneity in the target volume required smaller margins for motion compensation: margins of 2.5 mm, 2.4 mm and 1.3 mm were sufficient for compensation of 11.5 mm motion range and standard deviation of 3.9 mm in P105, P125 and P150, respectively. This effect of smaller margins for increased dose inhomogeneity was observed for all patients. Optimal sparing of the organ-at-risk surrounding the target was achieved for dose prescriptions P105 to P118. The internal target volume concept over-compensated breathing motion with higher than planned doses to the target and increased doses to the surrounding normal tissue.
Conclusion:
Treatment planning with inhomogeneous dose distributions in the target volume required smaller margins for compensation of breathing induced target motion with the consequence of lower doses to the surrounding organs-at-risk.

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Multiple window spatial registration error of a gamma camera: 133Ba point source as a replacement of the NEMA procedure

May 16th, 2009

Background:
The accuracy of multiple window spatial resolution characterises the performance of a gamma camera for dual isotope imaging. In the present study we investigate an alternative method to the standard NEMA procedure for measuring this performance parameter.
Methods:
A long-lived 133Ba point source with gamma energies close to 67Ga and a single bore lead collimator were used to measure the multiple window spatial registration error. Calculation of the positions of the point source in the images used the NEMA algorithm. The results were validated against the values obtained by the standard NEMA procedure which uses a liquid 67Ga source with collimation.
Results:
Of the source-collimator configurations under investigation an optimum collimator geometry, consisting of a 5 mm thick lead disk with a diameter of 46 mm and a 5 mm central bore, was selected. The multiple window spatial registration errors obtained by the 133Ba method showed excellent reproducibility (standard deviation < 0.07 mm). The values were compared with the results from the NEMA procedure obtained at the same locations and showed small differences with a correlation coefficient of 0.51 (p < 0.05). In addition, the 133Ba point source method proved to be much easier to use. A Bland-Altman analysis showed that the 133Ba and the 67Ga Method can be used interchangeably.
Conclusion:
The 133Ba point source method measures the multiple window spatial registration error with essentially the same accuracy as the NEMA-recommended procedure, but is easier and safer to use and has the potential to replace the current standard procedure.

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