Evaluation of the role of mitochondria in the non-targeted effects of ionizing radiation using cybrid cellular models.

Radiobiology is moving towards a better understanding of the intercellular signaling that occurs upon radiation and how its effects relate to the dose applied. The mitochondrial role in orchestrating this biological response needs to be further explored. Cybrids (cytoplasmic hybrids) are useful cell models for studying the involvement of mitochondria in cellular processes. In the present study we used cybrid cell lines to investigate the role of mitochondria in the response to radiation exposure. Cybrid cell lines, derived from the osteosarcoma human cell line 143B, harboring, either wild-type mitochondrial DNA (Cy143Bwt), cells with mitochondria with mutated DNA that causes mitochondrial dysfunction (Cy143Bmut), as well as cells without mitochondrial DNA (mtDNA) (143B-Rho0), were irradiated with 0.2 Gy and 2.0 Gy. Evaluation of the non-targeted (or bystander) effects in non-irradiated cells were assessed by using conditioned media from the irradiated cells. DNA double stranded breaks were assessed with the γH2AX assay. Both directly irradiated cells and cells treated with the conditioned media, showed increased DNA damage. The effect of the irradiated cells media was different according to the cell line it derived from: from Cy143Bwt cells irradiated with 0.2 Gy (low dose) and from Cy143Bmut irradiated with 2.0 Gy (high dose) induced highest DNA damage. Notably, media obtained from cells without mtDNA, the143B-Rho0 cell line, produced no effect in DNA damage. These results point to a possible role of mitochondria in the radiation-induced non-targeted effects. Furthermore, it indicates that cybrid models are valuable tools for radiobiological studies.

Optimization of skin dose using in-vivo MOSFET dose measurements in bolus/non-bolus fraction ratio: A VMAT and a 3DCRT study.

In-phantom and in-vivo three dimensional conformal radiation therapy (3DCRT) and volumetric modulated arc therapy (VMAT) skin doses, measured with and without bolus in a female anthropomorphic phantom RANDO and in patients, were compared against treatment planning system calculated values. A thorough characterization of the metal oxide semiconductor field effect transistor measurement system was performed prior to the measurements in phantoms and patients. Patients with clinical indication for postoperative external radiotherapy were selected. Skin dose showed higher values with 3DCRT technique compared with VMAT. The increase in skin dose due to the use of bolus was quantified. It was observed that, in the case of VMAT, the bolus effect on the skin dose was considerable when compared with 3DCRT. From the point of view of treatment time, bolus cost, and positioning reproducibility, the use of bolus in these situations can be optimized.

The use of needle holders in CTF guided biopsies as a dose reduction tool.

PURPOSE: The purpose of this study was to evaluate the efficacy of needle holders in reducing staff hand exposure during biopsies guided by computed tomography fluoroscopy (CTF), through the analysis of data acquired during a detailed monitoring study, undertaken in parallel with an ongoing optimization process to reduce hand irradiation. METHODS: Hand monitoring was performed with 11 extremity detectors, two per finger (base and tip) and one on the back of the wrist, for the left (dominant) hand, during two series of biopsies with comparable characteristics. The first series (47 biopsies) were performed with only quick-check method (QC) and occasional side-handle (SH) manipulation of the needle. The second series (63 biopsies) were performed after introducing needle holders (NH) in the course of an optimization process. RESULTS: Choice of technique (QC, QC + NH, QC + SH) by the interventional radiologist (IR) was related to biopsy difficulty. Measured hand exposure was low (< 1 mSv) for all QC-only procedures, and for most of the QC + NH procedures. Occasional side-handle manipulation still occurred during challenging biopsies, so that 8% of biopsies in the second series accounted for ~70% of total fingertip dose (~90 mSv). The methodology used allowed a detailed insight into the dose reduction achievable with needle holders during real procedures, without the limitations of phantom measurements. CONCLUSIONS: Needle holders proved effective in reducing mean hand exposure during clinical procedures where real-time manipulation was necessary. Occasional side-handle manipulation was found to contribute disproportionately to hand exposure. This highlights the importance of individual hand monitoring during CTF guided procedures.

Gafchromic XR-QA2 film as a complementary dosimeter for hand-monitoring in CTF-guided biopsies.

Computed tomography fluoroscopy (CTF) is a useful imaging technique to guide biopsies, particularly lung biopsies, but it also has the potential for very high hand exposures, despite use of quick-check method and needle holders whenever feasible. Therefore, reliable monitoring is crucial to ensure the safe use of CTF. This is a challenge, because ring dosimeters monitor exposure only at the base of one finger, while the fingertips may be exposed to the highly collimated CT beam. In this work we have explored the possibility of using Gafchromic XR-QA2 self-developing film as a complementary dosimeter to quantify hand exposure during CTF-guided biopsies. A glove used in a previous study and designed to contain 11 TLDs was adapted to include Gafchromic strips 7 mm wide, covering the fingers. A total of 22 biopsies were successfully performed wearing this GafTLD glove under sterile gloves, and the IR reported no difficulty or reduction of dexterity while wearing it. Comparison of dose distributions obtained from digitization of the Gafchromic film strips and absolute Hp(0.07) readings from TLDs showed good agreement, despite some positional uncertainty due to relative movement. Per procedure, doses at the base of the ring finger can be as low as 3%-8% of hand dose maximum. Accumulated dose at the base of the ring finger was four times lower than the dose maximum.

Characterization of geometric uncertainties of a dose calibrator during measurement of 90Y activity.

UNLABELLED: The performance and measurement of (90)Y with a dose calibrator has always been a key point of several international recommendations, specifically in the case of the radiopharmaceutical (90)Y-ibritumomab tiuxetan, among other applications, used in the treatment of non-Hodgkin lymphoma. The objective of the present work was to examine in detail some important sources of geometric errors that, if neglected, can lead to an increase in uncertainty about the measured activity of this ß(-) emitter radionuclide. METHODS: A CRC-15R dose calibrator was used to measure and quantify some of these sources, although the same methodology can easily be applied to any other similar equipment. The depth response along the main axis of the dose calibrator was carefully characterized, as well as syringe volume effects and source angular dependence. RESULTS: It was found that, if not taken properly into account, these issues can contribute to an increase in the activity uncertainty (e.g., 5.1% in the present example). This finding implies the possibility of easily reaching higher values than the internationally suggested 5% uncertainty in activity measurement for therapeutic purposes. CONCLUSION: These errors can be greatly reduced by previous characterization of the dose calibrator and careful implementation of the methodology for measurement.