| 1. |
- Hofving, Tobias, 1989, et al.
(författare)
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177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition
- 2019
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 26:4, s. 437-449
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Tidskriftsartikel (refereegranskat)abstract
- Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.
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| 2. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Evaluation of the impact of a system for real-time visualisation of occupational radiation dose rate during fluoroscopically guided procedures
- 2013
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Ingår i: Journal of Radiological Protection. - : IOP Publishing. - 0952-4746 .- 1361-6498. ; 33:3, s. 693-702
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Tidskriftsartikel (refereegranskat)abstract
- Optimisation of radiological protection for operators working with fluoroscopically guided procedures has to be performed during the procedure, under varying and difficult conditions. The aim of the present study was to evaluate the impact of a system for real-time visualisation of radiation dose rate on optimisation of occupational radiological protection in fluoroscopically guided procedures. Individual radiation dose measurements, using a system for real-time visualisation, were performed in a cardiology laboratory for three cardiologists and ten assisting nurses. Radiation doses collected when the radiation dose rates were not displayed to the staff were compared to radiation doses collected when the radiation dose rates were displayed. When the radiation dose rates were displayed to the staff, one cardiologist and the assisting nurses (as a group) significantly reduced their personal radiation doses. The median radiation dose (Hp(10)) per procedure decreased from 68 to 28 μSv (p = 0.003) for this cardiologist and from 4.3 to 2.5 μSv (p = 0.001) for the assisting nurses. The results of the present study indicate that a system for real-time visualisation of radiation dose rate may have a positive impact on optimisation of occupational radiological protection. In particular, this may affect the behaviour of staff members practising inadequate personal radiological protection.
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| 3. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Evaluation of the impact of a system for real-time visualisation of occupational radiation dose rate during fluoroscopically guided procedures
- 2013
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Ingår i: Nationellt möte om sjukhusfysik 2013, 13-14 november 2013, Varberg.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Optimisation of radiological protection for operators working with fluoroscopically guided procedures has to be performed during the procedure, under varying and difficult conditions. The aim of this study was to evaluate the impact of a system for real-time visualisation of radiation dose rate on optimisation of occupational radiological protection during fluoroscopically guided procedures. Individual radiation dose measurements, using a system for real-time visualisation, were performed in a cardiology laboratory for three cardiologists and ten assisting nurses. Radiation doses collected when the radiation dose rates were not displayed to the staff (period 1) were compared to radiation doses collected when the radiation dose rates were displayed (period 2). The results showed that when the radiation dose rates were displayed to the staff, one cardiologist and the assisting nurses (as a group) significantly reduced their personal radiation doses. The median radiation dose ((Hp(10)) per procedure decreased from 68 to 28 μSv (p=0.003) for this cardiologist and from 4.3 to 2.5 μSv (p=0.001) for the assisting nurses. The results of the present study indicate that a system for real-time visualisation of radiation dose rate may have a positive impact on optimisation of occupational radiological protection. In particular, this may affect the behaviour of staff members practising inadequate personal radiological protection.
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| 4. |
- Almén, Anja, 1964, et al.
(författare)
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OPTIMISATION OF OCCUPATIONAL RADIATION PROTECTION IN IMAGE-GUIDED INTERVENTIONS: EXPLORING VIDEO RECORDINGS AS A TOOL IN THE PROCESS
- 2016
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169:1-4, s. 425-429
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Tidskriftsartikel (refereegranskat)abstract
- The overall purpose of this work was to explore how video recordings can contribute to the process of optimising occupational radiation protection in image-guided interventions. Video-recorded material from two image-guided interventions was produced and used to investigate to what extent it is conceivable to observe and assess dose-affecting actions in video recordings. Using the recorded material, it was to some extent possible to connect the choice of imaging techniques to the medical events during the procedure and, to a less extent, to connect these technical and medical issues to the occupational exposure. It was possible to identify a relationship between occupational exposure level to staff and positioning and use of shielding. However, detailed values of the dose rates were not possible to observe on the recordings, and the change in occupational exposure level from adjustments of exposure settings was not possible to identify. In conclusion, the use of video recordings is a promising tool to identify dose-affecting instances, allowing for a deeper knowledge of the interdependency between the management of the medical procedure, the applied imaging technology and the occupational exposure level. However, for a full information about the dose-affecting actions, the equipment used and the recording settings have to be thoroughly planned.
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| 5. |
- Almén, Anja, 1964, et al.
(författare)
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Optimisation of occupational radiological protection in image-guided interventions: potential impact of dose rate measurements.
- 2015
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Ingår i: Journal of radiological protection : official journal of the Society for Radiological Protection. - : IOP Publishing. - 1361-6498. ; 35:1, s. 47-62
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Tidskriftsartikel (refereegranskat)abstract
- The optimisation of occupational radiological protection is challenging and a variety of factors have to be considered. Physicians performing image-guided interventions are working in an environment with one of the highest radiation risk levels in healthcare. Appropriate knowledge about the radiation environment is a prerequisite for conducting the optimisation process. Information about the dose rate variation during the interventions could provide valuable input to this process. The overall purpose of this study was to explore the prerequisite and feasibility to measure dose rate in scattered radiation and to assess the usefulness of such data in the optimisation process.Using an active dosimeter system, the dose rate in the unshielded scattered radiation field was measured in a fixed point close to the patient undergoing an image-guided intervention. The measurements were performed with a time resolution of one second and the dose rate data was continuously timed in a data log. In two treatment rooms, data was collected during a 6month time period, resulting in data from 380 image-guided interventions and vascular treatments in the abdomen, arms and legs. These procedures were categorised into eight types according to the purpose of the treatment and the anatomical region involved.The dose rate varied substantially between treatment types, both regarding the levels and the distribution during the procedure. The maximum dose rate for different types of interventions varied typically between 5 and 100mSvh(-1), but substantially higher and lower dose rates were also registered. The average dose rate during a complete procedure was however substantially lower and varied typically between 0.05 and 1mSvh(-1). An analysis of the distribution disclosed that for a large part of the treatment types, the major amount of the total accumulated dose for a procedure was delivered in less than 10% of the exposure time and in less than 1% of the total procedure time.The present study shows that systematic dose rate measurements are feasible. Such measurements can be used to give a general indication of the exposure level to the staff and could serve as a first risk assessment tool when introducing new treatment types or x-ray equipment in the clinic. For example, it could provide an indication for when detailed eye dose measurements are needed. It also gives input to risk management considerations and the development of efficient routines for other radiological protection measures.
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| 6. |
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| 7. |
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| 8. |
- Magee, Jill S, et al.
(författare)
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Derivation and application of dose reduction factors for protective eyewear worn in interventional radiology and cardiology.
- 2014
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Ingår i: Journal of radiological protection : official journal of the Society for Radiological Protection. - : IOP Publishing. - 1361-6498. ; 34:4, s. 811-823
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Tidskriftsartikel (refereegranskat)abstract
- Doses to the eyes of interventional radiologists and cardiologists could exceed the annual limit of 20mSv proposed by the International Commission on Radiological Protection. Lead glasses of various designs are available to provide protection, but standard eye dosemeters will not take account of the protection they provide. The aim of this study has been to derive dose reduction factors (DRFs) equal to the ratio of the dose with no eyewear, divided by that when lead glasses are worn. Thirty sets of protective eyewear have been tested in x-ray fields using anthropomorphic phantoms to simulate the patient and clinician in two centres. The experiments performed have determined DRFs from simulations of interventional procedures by measuring doses to the eyes of the phantom representing the clinician, using TLDs in Glasgow, Scotland and with an electronic dosemeter in Gothenburg, Sweden. During interventional procedures scattered x-rays arising from the patient will be incident on the head of the clinician from below and to the side. DRFs for x-rays incident on the front of lead glasses vary from 5.2 to 7.6, while values for orientations similar to those used in the majority of clinical practice are between 1.4 and 5.2. Specialised designs with lead glass side shields or of a wraparound style with angled lenses performed better than lead glasses based on the design of standard spectacles. Results suggest that application of a DRF of 2 would provide a conservative factor that could be applied to personal dosemeter measurements to account for the dose reduction provided by any type of lead glasses provided certain criteria relating to design and consistency of use are applied.
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| 9. |
- Martin, Colin, et al.
(författare)
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Eye dosimetry and protective eyewear for interventional clinicians
- 2015
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 165:1-4, s. 284-288
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Tidskriftsartikel (refereegranskat)abstract
- Doses to the eyes of interventional clinicians can exceed 20 mSv. Various protective devices can afford protection to the eyes with the final barrier being protective eyewear. The protection provided by lead glasses is difficult to quantify, and the majority of dosimeters are not designed to be worn under lead glasses. This study has measured dose reduction factors (DRFs) equal to the ratio of the dose with no protection, divided by that when lead glasses are worn. Glasses have been tested in X-ray fields using anthropomorphic phantoms to simulate the patient and clinician. DRFs for X-rays incident from the front vary from 5.2 to 7.6, while values for orientations reminiscent of clinical practice are between 1.4 and 5.2. Results suggest that a DRF of two is a conservative factor that could be applied to personal dosimeter measurements to account for the dose reduction provided by most types of lead glasses.
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| 10. |
- Saadati, Sofia, 1992, et al.
(författare)
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Binding and internalization of 177Lu-octreotate in human tumor cell lines of different origin
- 2017
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Ingår i: 63rd Annual Meeting of the Radiation Research Society, Cancun, Mexico.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-octreotate is used for systemic treatment of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumors (NETs), mainly for small-intestine NETs and endocrine pancreatic tumors. Further research is needed to evaluate the possibility of using this type of treatment in patients with other SSTR-expressing tumors. Tumor binding and uptake of the radiopharmaceutical is highly dependent on SSTR expression. In order to determine the potential of using 177Lu-octreotate for treatment of other tumor cell lines, in vitro studies of binding and internalization are needed. The aim of this study was to asses binding and internalization of 177Lu-octreotate in various cancer cell lines and compare with our previous results. In vitro studies were performed on neuroblastoma (CLB-BAR, IMR-32), lung adenocarcinoma (h1975, h2228) and invasive breast carcinoma (BT474, MCF-7, MDA-MB-231, MDA-MB-361, T47D, ZR-75-1) cell lines. Cell cultures were incubated with low or high amounts of 177Lu-octreotate. To block SSTR and thereby determine the specific uptake, control groups were incubated with 177Lu-octreotate and excess octreotide. The amount of unbound, membrane-bound, and internalized 177Lu in each sample was determined after 24 h. Several of the studied tumor cell lines showed specific binding of 177Lu-octreotate. The highest binding and internalization after 24 h was seen for the neuroblastoma cell lines IMR-32 (58% internalized, 9.4% membrane-bound) and CLB-BAR (26% internalized, 3.4% membrane-bound). Specific binding was also found in some breast cancer cell lines (e.g. 3.1% internalized, 0.5% membrane-bound in MDA-MB-361). No specific binding was found in lung adenocarcinoma. In comparison with our previous findings in NET and NET-like cell lines, these results indicate that SSTR-based PRRT may be a potential treatment option for patients with neuroblastoma and certain types of breast cancer. Promising results showing specific tumor uptake of 177Lu-octreotate were obtained for SSTR-expressing tumor cell lines in vitro, indicating the possibility of using SSTR-based diagnostic and therapeutic regimes on more tumor types than those in current clinical practice.
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