| 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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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Combination therapy of medullary thyroid cancer using radiation and vandetanib
- 2017
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. Annual Congress of the European Association of Nuclear Medicine October 21 – 25, 2017 Vienna, Austria. Vol. 44, Suppl. 2. EP-0792. - : Springer. - 1619-7070 .- 1619-7089.
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION Most patients diagnosed with medullary thyroid cancer (MTC) present with metastatic disease. MTC are rare neuroendocrine tumours that occur either sporadically or in a hereditary form. Surgical resection of the thyroid gland followed by external beam radiotherapy (EBRT) or the use of tyrosine kinase inhibitors are current clinical methods for management of MTC. Unfortunately, the 10-year survival for patients with metastatic disease is only about 40%. However, many MTC tumours overexpress somatostatin receptors as molecular targets. Therefore, one option for patients with MTC is systemic treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) that bind with high affinity and specificity to somatostatin receptors on the tumour cells. In addition, the tyrosine kinase inhibitor vandetanib has recently been approved for single-agent treatment of MTC by the U.S. Food and Drug Administration (FDA). The aim of this study was to investigate the potential synergistic effect of combining irradiation and vandetanib for treatment of MTC. SUBJECTS & METHODS BALB/c nude mice were transplanted with patient-derived MTC cells (GOT2). When developed tumours reached a volume of about 500 mm3, the mice were treated with EBRT, vandetanib or a combination of both. The radiation dose and the amount of vandetanib were chosen to give moderate effect as single treatment to enable detection of any increased effect from the combination. Tumour volume was followed and compared with that in untreated mice. RESULTS We found that the largest treatment effect over time was seen for the animals receiving a combination of both EBRT and vandetanib. Given as single-agent treatment, EBRT and vandetanib resulted in a reduction in tumour size or in tumour growth arrest. For example, at two weeks after start of treatment, the tumour volume was reduced by 64%, 52%, and 73% compared with the untreated control group, for the animals treated with single EBRT, single vandetanib, and the combination, respectively. CONCLUSION The results indicate that an additive or even synergistic effect could be achieved when combining irradiation with vandetanib for treatment of patients with MTC. Further studies are needed to investigate the possibility of using 177Lu-octreotate for treatment of MTC, both as single-agent treatment or in combination with vandetanib.
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| 16. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Determination of 177Lu-octreotate activity concentration in vivo using intraoperative gamma probes - a comparative study
- 2015
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Ingår i: Cancerfondens planeringsgrupp för onkologisk radionuklidterapis vintermöte 2015, 22-23 januari, Umeå, Sverige..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION Radionuclide therapy using 177Lu-octreotate has shown promising results for patients with metastasised neuroendocrine (NE) tumours. However, complete remission is achieved only in a few patients due to healthy limiting organs, e.g. kidneys and bone marrow. A new treatment method of NE liver metastases is under development at our facility, based on local administration of 177Lu-octreotate to the liver. However, this method requires the possibility to quantify activity concentration in vivo. Intraoperative gamma probes are routinely used for radio-guided surgery and localisation of diagnostic radionuclides. The aim of this study was to evaluate whether intraoperative gamma probes could be used to determine 177Lu activity concentration in vivo. METHODS Important performance parameters were acquired for two intraoperative gamma probes using different sources of 177Lu, in order to compare the characteristics of the probes. Point sources were used for determination of the range for linear response, and the spatial resolution (FWHM) was evaluated by measuring the line profile over a line source at different depths in a phantom of tissue equivalent plastic. To investigate the ability of the probes to distinguish between normal and tumour tissue, a clinical situation was simulated by creating an agarose gel phantom. This phantom contained a homogenous distribution of 177Lu of a low activity concentration, simulating normal tissue. To simulate metastases, hot gel spheres (5-20 mm), containing a higher activity concentration, were added to the phantom. RESULTS The point source measurements demonstrated great differences between the two probes; one probe showed saturation of the signal at much lower activities than the other. The spatial resolution (FWHM) increased from about 10 to 100 mm when the depth of the line source was increased from 0 to 80 mm. One probe showed lower values of FWHM than the other, for all depths. The measurements using the agarose gel phantom showed high ratios between count rates measured over the hot gel spheres and over the background, for both probes. These results indicated a good ability to distinguish between normal and tumour tissue. CONCLUSION The two evaluated gamma probes showed differences in technical performance. However, satisfying results were obtained for both probes, indicating that intraoperative gamma probe measurements are feasible for determination of 177Lu activity concentration in vivo.
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| 17. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Evaluation of eye lens doses received by medical staff working in interventional radiology at sahlgrenska university hospital
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Background: The International Commission on Radiological Protection (ICRP) recently lowered their recommended occupational eye lens dose limit from 150 mSv in a year to 20 mSv in a year, averaged over a defined period of 5 years. Aim: The main aim of the present study was to investigate the eye lens doses received by the interventional staff at Sahlgrenska University Hospital. Another aim was to evaluate whether the dose recorded by the PDM, a dosimeter worn at thorax height, could be used as an indicator of eye lens dose. Material and Methods: To prepare for the personnel eye lens dose assessments, phantom measurements were carried out. These preparations included deciding the optimal position of an eye lens dosimeter, evaluation of different models of lead glasses and estimation of a ratio between the eye lens dose and the dose recorded by the PDM. Personnel eye lens doses were assessed using TL-dosimeters held by individual headbands worn by staff members at the Catheterization Laboratory at the department of Cardiology and at the division of Peripheral Interventional Radiology at the department of Radiology at Sahlgrenska University Hospital for one month. Staff members also wore a PDM at thorax height outside their lead apron. Results and Discussion: Materials with an equivalent lead thickness of 0.75 mm block over 95% of incident radiation but the lead glasses evaluated (0.75 mm) reduced the eye lens dose by only 30-88% due to radiation back scattered in the head and oblique incident radiation. Many operators reported annual eye lens doses of over 10 mSv. The eye lens doses of nurses were generally much lower. The ratios between equivalent doses recorded by TLD and PDM were as expected higher for nurses than for operators but the ratios varied also between different operators. Conclusions: The estimations of annual doses have uncertainties and the lens doses of operators are high enough to cause concern. Based on the results of the present study, operators might be recommended to wear lead glasses in the future. Estimating eye lens dose from the dose recorded by the PDM is difficult. This method includes large uncertainties. The PDM should instead be used to indicate whether a more precise measurement is necessary.
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| 18. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Evaluation of the possibility of using intraoperative gamma probe measurements for determining 177Lu-octreotate activity concentration in vivo
- 2014
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Ingår i: 27th Annual Congress on European Association of Nuclear Medicine, Gothenburg, Sweden, October 18-22, 2014..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION Intraoperative gamma probes are routinely used for radio-guided surgery, primarily sentinel node mapping or localization of small tumors after injection of a diagnostic radiopharmaceutical, labelled with e.g. 99mTc or 111In. For therapy purposes, treatment of neuroendocrine (NE) tumors using the beta emitting radiopharmaceutical 177Lu-octreotate has shown promising results, with kidneys and red bone marrow as limiting organs. A new treatment method using 177Lu-octreotate for liver metastases is under development at our facility. For this development, a method to determine the activity concentration of 177Lu-octreotate in tumor and normal tissues in vivo during surgery is required. The aim of this study was therefore to evaluate whether an intraoperative gamma probe could be suitable for this purpose. METHODS Essential detector characteristics were acquired for two intraoperative gamma probes using different sources containing 177Lu. The range for linear response was determined using point sources of increasing activity. Spatial resolution (full width at half maximum, FWHM) and efficiency were determined, using a line source placed at different depths in a tissue equivalent plastic phantom, by moving each probe perpendicularly over the line source. To simulate a clinical situation, tumor phantoms were designed, consisting of agarose gel spheres (5–20 mm diameter) at the surface of a water background. The gel spheres, simulating tumors, contained a high activity concentration of 177Lu while the water, simulating normal tissue, contained a background activity concentration of 177Lu. Count rates were measured using the gamma probes in order to investigate the possibility to distinguish between normal and tumor tissue. RESULTS A linear response (within ±10 %) was seen for point source activities between 1–30 MBq, corresponding to count rates in the detectors of about 100–4,000 counts per second (cps). FWHM increased from about 10 to 70 mm when the depth of the line source increased from 0 to 80 mm. In the tumor phantom measurements, high ratios between count rates measured over the gel sphere and over the water background were acquired, indicating a good ability to distinguish between normal and tumor tissue. CONCLUSION An intraoperative gamma probe could be a useful tool for measurements of activity concentration of 177Lu-octreotate in tissues in vivo.
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| 19. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Evaluation of two intraoperative gamma detectors for assessment of 177Lu activity concentration in vivo
- 2017
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered 177Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering 177Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the 177Lu activity concentration in tissues in vivo. The aim of this study was to evaluate different performance parameters of two commercially available intraoperative gamma detectors in order to investigate whether intraoperative gamma detector measurements could be used to determine 177Lu activity concentration in vivo. Results Measurements were made using different sources containing 177Lu. Response linearity, sensitivity, spatial resolution and its depth dependence, organ thickness dependence of the measured count rate and tumour detectability were assessed for two intraoperative gamma detectors. The two detectors (a scintillation and a semiconductor detector) showed differences in technical performance. For example, the sensitivity was higher for the scintillation detector, while the spatial resolution was better for the semiconductor detector. Regarding organ thickness dependence and tumour detectability, similar results were obtained for both detectors, and even relatively small simulated tumours of low tumour-to-background activity concentration ratios could be detected. Conclusions Acceptable results were obtained for both detectors, although the semiconductor detector proved more advantageous for our purpose. The measurements demonstrated factors that must be corrected for, such as organ thickness or dead-time effects. Altogether, intraoperative gamma detector measurements could be used to determine 177Lu activity concentration in vivo.
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| 20. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Gemcitabine potentiates the anti-tumour effect of radiation on medullary thyroid cancer.
- 2019
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- Patients with medullary thyroid cancer (MTC) are often diagnosed with spread tumour disease and the development of better systemic treatment options for these patients is important. Treatment with the radiolabelled somatostatin analogue 177Lu-octreotate is already a promising option but can be optimised. For example, combination treatment with another substance could increase the effect on tumour tissue. Gemcitabine is a nucleoside analogue that has been shown to sensitise tumour cells to radiation. The aim of this study was to investigate potentially additive or synergistic effects of combining radiation with gemcitabine for treatment of MTC. Nude mice transplanted with patient-derived MTC tumours (GOT2) were divided into groups and treated with radiation and/or gemcitabine. Radiation treatment was given as 177Lu-octreotate or external beam radiotherapy (EBRT). The volume of treated and untreated tumours was followed. The absorbed dose and amount of gemcitabine were chosen to give moderate tumour volume reduction when given as monotherapy to enable detection of increased effects from combination treatment. After follow-up, the mice were killed and tumours were immunohistochemically (IHC) analysed. Overall, the animals that received a combination of EBRT and gemcitabine showed the largest reduction in tumour volume. Monotherapy with EBRT or gemcitabine also resulted in a clear detrimental effect on tumour volume, while the animals that received 177Lu-octreotate monotherapy showed similar response as the untreated animals. The GOT2 tumour was confirmed in the IHC analyses by markers for MTC. The IHC analyses also revealed that the proliferative activity of tumour cells was similar in all tumours, but indicated that fibrotic tissue was more common after EBRT and/or gemcitabine treatment. The results indicate that an additive, or even synergistic, effect may be achieved by combining radiation with gemcitabine for treatment of MTC. Future studies should be performed to evaluate the full potential of combining 177Lu-octreotate with gemcitabine in patients.
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| 21. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Gemcitabine potentiates the anti-tumour effect of radiation therapy on medullary thyroid cancer
- 2016
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Ingår i: 4th Swedish Cancer Research Meeting, 7-8 november 2016, Gothenburg, Sweden..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND Most patients diagnosed with medullary thyroid cancer (MTC) present with metastatic disease and the 10-year survival for these patients is only about 40%. Since many MTCs overexpress somatostatin receptors, one option for these patients is systemic treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate). In addition, the nucleoside gemcitabine has shown anti-tumour activity in MTC. The aim of this study was to investigate potential synergistic effects of combining gemcitabine with irradiation for treatment of MTC. MATERIALS & METHODS Nude mice carrying a patient-derived MTC (GOT2) was divided into treatment groups. They received radiation therapy (as external beam radiotherapy (EBRT) or 177Lu-octreotate) and gemcitabine both as single-agent treatment and in combination. The radiation dose and the amount of gemcitabine were kept low to enable detection of any synergistic effects. Tumour volume was followed and compared with that in untreated mice. RESULTS The largest treatment effect was seen for the animals receiving a combination of both EBRT and gemcitabine. Given as single-agent treatment, both EBRT and gemcitabine resulted in a reduction in tumour growth arrest or even a reduction in tumour volume. The animals treated with only 177Lu-octreotate showed similar response as the control group. CONCLUSIONS It is possible that an additive or even synergistic effect on tumour tissue would be achieved when combining gemcitabine with irradiation for treatment of patients with MTC. Further studies should be performed to evaluate the possibility of using 177Lu-octreotate for treatment of MTC, both as single-agent treatment or in combination with gemcitabine.
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| 22. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Increased therapeutic effect on medullary thyroid cancer using a combination of radiation and tyrosine kinase inhibitors : Increased effect on medullary thyroid cancer by combining radiation with tyrosine kinase inhibitors
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Since patients with medullary thyroid cancer (MTC) often have metastatic disease at the time of diagnosis, the development of efficient systemic treatment options for MTC is important. Vandetanib and cabozantinib are two tyrosine kinase inhibitors (TKIs) that were recently approved by FDA and EMA for systemic treatment of metastatic MTC. Additionally, since MTC is of a neuroendocrine tumour type, treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) is a valid option for patients with MTC. The aim of this study was to investigate the potentially increased therapeutic effect of combining radiation therapy with these TKIs for treatment of MTC in a mouse model. Nude mice carrying patient-derived MTC tumours (GOT2) were treated with external beam radiotherapy (EBRT) and/or one of the two TKIs vandetanib or cabozantinib. The tumour volume was determined and compared with that of mock-treated controls. The treatment doses were chosen to give a moderate effect as monotherapy to be able to detect any increased therapeutic effect from the combination therapy. At the end of follow-up, tumours were processed for immunohistochemical (IHC) analyses. The animals in the combination therapy groups showed the largest reduction in tumour volume and the longest time to tumour progression. Two weeks after start of treatment, the tumour volume for these mice was reduced by about 70-75% compared with controls. Furthermore, also EBRT and TKI monotherapy resulted in a clear anti-tumour effect with a reduced tumour growth compared with controls. The results show that an increased therapeutic effect could be achieved when irradiation is combined with TKIs for treatment of MTC. Future studies should evaluate the potential of using 177Lu-octreotate therapy in combination with TKIs in patients.
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| 23. |
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| 24. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Local treatment of liver metastases by administration of 177Lu-octreotate via isolated hepatic perfusion – A preclinical simulation of a novel treatment strategy
- 2019
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Ingår i: Surgical Oncology. - : Elsevier BV. - 0960-7404. ; 29, s. 148-156
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Systemic 177Lu-octreotate treatment for metastatic neuroendocrine tumours is restricted by organs at risk. By administering 177Lu-octreotate during isolated hepatic perfusion (IHP), the uptake in organs at risk might be strongly reduced. The aim of this study was to investigate the feasibility to use the combination of IHP and radionuclide therapy. Methods. To simulate IHP, the liver of a pig was prepared for ex vivo perfusion. Blood containing 490 MBq 177Lu-octreotate was circulated through the liver for 60min, after which the liver was rinsed. After IHP, the liver was examined by SPECT/CT. Lastly, an intraoperative gamma detector (IGD) was used to determine 177Lu activity concentration in the liver and results were compared with the activity concentration in corresponding liver biopsies. Results. Detector measurements over the liver during the IHP showed a fast increase with a maximum after approximately 10–15min. After IHP, about 75% of the 177Lu in the liver could be washed out. The SPECT/CT images revealed a relatively inhomogeneous distribution. Nevertheless, the IGD values of 177Lu activity concentration showed acceptable agreement with the biopsy values. Conclusions. Our results in pig show that it could be feasible to treat patients with liver metastases from NETs with 177Lu-octreotate via IHP 177. However, an inhomogeneous distribution of 177Lu-octreotate in normal liver tissue is expected, and in order to determine the activity concentration with satisfactory accuracy using an IGD, measurements need to be performed at several positions over the liver.
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| 25. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Mätmetoder för bestämning av stråldoser till ögats lins
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I april 2011 sänkte International Commission on Radiological Protection (ICRP) sin rekommenderade dosgräns för ögats lins för arbetstagare vid verksamhet med joniserande strålning från 150 mSv/år till 20 mSv/år (ekvivalent dos). Under senare år har det i flera studier gjorts uppskattningar av ekvivalent dos till ögats lins för per-sonal som arbetar med röntgenvägledda procedurer. Resultaten från de flesta av dessa tyder på att det finns risk att personal överstiger 20 mSv/år till ögats lins. Hp(3) (persondosekvivalenten på 3 mm djup i mjuk vävnad) är den, av International Commission on Radiation Units and Measurements (ICRU), föreslagna storheten för att uppskatta ekvivalent dos till ögats lins. Konversionsfaktorer från luftkerma till Hp(3) finns i dag inte tillgängliga i någon internationell standard. För mätningar av persondosekvivalent till ögats lins används därför ofta Hp(0,07) istället. Aktiva dosimetrar (exempelvis EDD-30, NED-30, RaySafe i2, DMC 3000 eller EPD) kan användas för grov initial uppskattning av ekvivalent dos till extremiteter eller ögats lins. För att minska osäkerheter i samband med mätning bör passiva do-simetrar användas (exempelvis DIS-1, EYE-DTM, Inlight® nanoDotTM eller ett TLD-system). Om det tillgängliga mätinstrumentet inte är kalibrerat för relevant energi och djup samt med lämpligt fantom för den önskvärda tillämpningen bör det övervägas att utföra kalibreringen på annat sätt. Om lokal kalibrering av mätinstrument inte är möjligt kan de skickas in till SSM:s riksmätplats för joniserande strålning. SSM erbjuder spårbar kalibrering av mätinstrument i strålfält i ISO:s N-serie enligt ISO 4037. Operatörens position i förhållande till patient och röntgenrör ser olika ut för olika typer av röntgenvägledda procedurer. Vid vissa typer av procedurer inom kardiologi träffar dock den spridda strålningen nästan uteslutande operatörens ögon snett ner-ifrån vänster. Energiintervallet för den spridda strålningen som träffar operatören vid en röntgenvägledd procedur är ungefär 20–100 keV. Då primärstrålningen träffar patienten och sprids mot operatören vid röntgenvägledda procedurer förskjuts energispektrumet ungefär 10 keV mot lågenergiområdet. Felaktig positionering eller kalibrering av en dosimeter avsedd för uppskattning av ekvivalent dos till ögats lins leder till mätfel. För personal som arbetar med röntgen-vägledda procedurer bör dosimetern vara kalibrerad att mäta Hp(0,07) eller Hp(3). Att använda Hp(10) leder till större osäkerheter. Vad gäller positioneringen bör dosimetern placeras på tinningen bredvid ögat, så nära ögat som möjligt, på den sida röntgenröret befinner sig. Det är viktigt att vara medveten om vilka osäkerheter som förknippas med olika mätmetoder. Så länge man är medveten om osäkerheterna kan flera olika metoder användas för uppskattning av ekvivalent dos till ögats lins, det beror på vilket syfte mätningen har. Under arbetet med denna rapport har en del forskningsbehov identifierats, enligt följande. För att få en ökad kunskap om samband mellan exponering och hälsoeffekter behövs sannolikt en ökad kunskap om energideponering i ögat som organ för olika typer av strålningssituationer. De skyddsstorheter som beskrivs i denna rapport används ibland också i studier vars syfte är att kartlägga effekter av bestrålning, exempelvis i epidemiologiska studier. Skyddsstorheterna är en oexakt beskrivning av energideponering i olika delar av ögat. Rimligtvis kan en ökad kunskap om grundläggande dosimetri för olika energier och strålslag bidra till att osäkerheterna minskar i studier där effekter kartläggs. Även utredningsarbete om konsekvenser av en sänkt dosgränser behövs. Detta gäller såväl metoder för att kontrollera att dosimetrar uppfyller de krav som i dag ställs och att använda metoder i kliniken genererar tillräckligt noggranna värden för att säkerställa att dosgränser inte överskrids.
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| 26. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Radiolabelled pharmaceuticals MIBG and octreotate for treatment of metastatic pheochromocytoma and paraganglioma
- 2014
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Ingår i: SweRays Workshop, Malmö, Sweden, Aug 20-22, 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The 5-year survival for patients with metastatic pheochromocytoma (PC) and paraganglioma (PGL) is less than 50%. There is a clear need for development of better diagnostic and therapeutic options for these patients. Radionuclide therapy offers the possibility to treat spread PC/PGL. The norepinephrine (NE) analogue metaiodobenzylguanidine (MIBG) and the somatostatin (SST) analogues octreotate or octreotide are possible molecules that could be used for this purpose. These analogues have different biodistribution and different organs at risk, when used for therapy. Thus, combined therapy, using both radiolabelled NE and SST analogues, might be beneficial for these patients. Aim: The aim of this study was to evaluate the possibility of using 177Lu-octreotate and/or 131I-MIBG for treatment of patients with metastatic PC/PGL. Materials and Methods: Three patients with metastatic PC/PGL were injected with 131I-MIBG and 111In-octreotide, and four patients with metastatic PC/PGL were injected with 111In-octreotide, before surgical removal of the primary tumour. During surgery, tissue samples of tumour, blood, fat and muscle were collected and weighed, and the radioactivity was measured in a gamma counter. The activity concentration in these tissue samples was then calculated for each radionuclide. Additionally, tumour-to-blood activity concentration ratios (T/B) were calculated. Results: The activity concentrations and T/B values showed large variations between patients. For 111In-octreotide, T/B values were 25-590 and for 131I-MIBG, the corresponding values were 0-1600. Conclusion: The sometimes high T/B values show a clear possibility of using 177Lu-octreotate and 131I-MIBG for treatment of some patients with metastatic PC/PGL. However, due to the large variation between patients, individual investigation of tumour uptake prior to treatment is required.
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| 27. |
- Sandblom, Viktor, 1987
(författare)
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Strategies for optimisation of 177Lu-octreotate therapy – exploring local administration and combination therapy regimens
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroendocrine tumours (NETs) are a group of heterogeneous tumour types that originate in hormone-producing organs. Patients with NETs are often diagnosed after the primary tumour has metastasised. One treatment option for these patients that has shown very promising results is systemic treatment using the radiolabelled somatostatin analogue 177Lu-octreotate. However, the outcome of this treatment is currently restricted by healthy organs at risk. The aim of this work was to optimise 177Lu-octreotate therapy of NETs by investigating strategies based on local administration and on combination therapy regimens. The feasibility of local treatment of liver metastases was evaluated by administering 177Lu-octreotate via isolated hepatic perfusion (IHP) in a pig animal model. During IHP, the liver was completely isolated from the systemic circulation. An intraoperative gamma detector was evaluated for the purpose of determining 177Lu activity concentration in vivo during treatment. This detector was also evaluated by assessment of its technical performance parameters using phantoms. In summary, the results showed that it could be feasible to treat patients with liver metastases from NETs with 177Luoctreotate via IHP. A relatively inhomogeneous uptake was obtained and to accurately quantify 177Lu activity concentration using an intraoperative gamma detector, measurements may need to be performed at several positions over the liver. In the combination therapy experiments, nude mice transplanted with NETs were treated with radiation therapy alone (as 177Lu-octreotate or external beam radiotherapy) and in combination with one of the drugs gemcitabine, vandetanib, cabozantinib, or ganetespib. After treatment, tumour volume was followed and compared with that in control mice. Overall, combination treatment resulted in the largest decrease in tumour volume and the longest time to progression. The results indicated that additive, and sometimes synergistic, effects could be obtained when combining 177Luoctreotate with another drug for treatment of patients with NETs.
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| 28. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Treatment of medullary thyroid cancer using a combination of radiation and gemcitabine
- 2016
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Ingår i: 62nd Annual International Meeting Radiation Research Society 2016. Big Island, Hawaii, USA, October 16-19, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION Medullary thyroid cancer (MTC) is a very rare type of cancer and patients often present with metastatic disease at the time of diagnosis. In contrast to other types of thyroid cancers, MTC originates from C-cells and therefore lacks the iodine pump NIS. This means that MTC cannot be treated with radioiodine, which otherwise is a common systemic treatment method for thyroid cancer. Instead, the use of radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) might be an option, since many MTCs overexpress somatostatin receptors. Furthermore, the nucleoside analogue gemcitabine has previously been used to treat MTC. The aim of this study was to investigate potential synergistic effects of combining irradiation with gemcitabine for treatment of MTC. METHODS The patient-derived MTC cell line GOT2 was transplanted to BALB/c nude mice, which received radiation therapy alone, gemcitabine alone or a combination of both. Radiation therapy was given either as external beam radiotherapy or as i.v. injection of 177Lu-octreotate. The tumour volume was followed and compared with that in untreated mice. The radiation dose and the amount gemcitabine were chosen to give low treatment effect as single treatment to enable detection of any additive or synergistic effects. RESULTS Overall, the animals receiving a combination of both external beam radiotherapy and gemcitabine showed the largest reduction in tumour size over time. Both gemcitabine and external beam radiotherapy alone gave a clear detrimental effect on tumour growth compared with the control group, while the animals receiving only 177Lu-octreotate showed similar response as the control group, possibly due to a too low amount of injected activity. CONCLUSION The results indicate that an additive or even synergistic effect can be achieved by combining radiation with gemcitabine for treatment of MTC. Further studies should be made evaluating the full potential of combining gemcitabine with 177Lu-octreotate.
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| 29. |
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| 30. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Tyrosinkinashämmare kan öka effekten från strålbehandling av medullär tyreoideacancer
- 2019
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Ingår i: Nationellt möte om sjukhusfysik.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- SYFTE Medullär tyreoideacancer (MTC) är en neuroendokrin cancertyp som har sitt ursprung i sköldkörtelns hormonproducerande C-celler. Många MTC överuttrycker receptorer för somatostatin vilket möjliggör radionuklidterapi med exempelvis 177Lu-oktreotat. Få patienter botas dock helt och optimering av behandlingen behövs. Ett sätt att optimera behandlingen är att kombinera 177Lu-oktreotat med ett annat läkemedel i syfte att öka effekten från strålningen. Nyligen godkändes två tyrosinkinashämmare (vandetanib och cabozantinib) för behandling av MTC. Syftet med denna studie var att undersöka ifall en ökad effekt kan fås då strålbehandling kombineras med tyrosinkinashämmare för behandling av MTC. METOD Nakna möss (BALB/c) transplanterades med humana MTC-celler (GOT2) och behandlades med extern strålbehandling och/eller tyrosinkinashämmare. Behandlings-effekten, som tumörvolym efter behandling, jämfördes med den hos obehandlade möss. För att möjliggöra detektion av en eventuellt ökad behandlingseffekt hos de möss som fick kombinationsbehandling (både strålbehandling och tyrosinkinas¬hämmare) valdes den absorberade dosen och mängden läkemedel så att en suboptimal effekt erhölls då respektive behandling gavs som singelbehandling. RESULTAT Kombinationsbehandling resulterade i störst minskning av tumörvolym och längst tid till progression. Exempelvis hade tumörvolymen hos de möss som fick kombinationsbehandling minskat med ca 70-75% efter två veckor jämfört med obehandlade möss. Även som singelbehandling resulterade båda behandlingar i en tydlig effekt på tumörvolymen, med en minskning på ca 50-65% efter två veckor. KONKLUSIONER Effekten från strålbehandling av möss med MTC-tumörer kan ökas genom kombinationsbehandling med tyrosinkinashämmare. Framtida studier bör utvärdera möjligheten att använda en kombination av 177Lu-oktreotat och tyrosinkinashämmare för behandling av patienter med MTC.
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| 31. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Vandetanib may act as radiosensitiser for 177Lu-octreotate treatment of medullary thyroid cancer
- 2018
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Ingår i: 2nd European Congress of Medical Physics. Physica Medica Vol. 52, Suppl. 1, pp. 62-63. - : Elsevier BV. - 1120-1797.
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Konferensbidrag (refereegranskat)abstract
- PURPOSE: Medullary thyroid cancer (MTC) is a very rare type of cancer. Most patients diagnosed with MTC present with metastatic disease. Therefore, surgical resection is often complemented by external beam radiotherapy (EBRT) or the use of tyrosine kinase inhibitors. In order to reach distant metastases, systemic therapy is needed. Vandetanib is a tyrosine kinase inhibitor that was recently approved for single-agent treatment of MTC by the U.S. Food and Drug Administration (FDA). Additionally, since many MTC overexpress somatostatin receptors, radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) offer a promising treatment option for patients with MTC. The aim of this study was to investigate the potential synergistic effect of combining irradiation and vandetanib for treatment of MTC. METHODS: BALB/c nude mice were transplanted with patient-derived MTC cells (GOT2) and treated with EBRT alone, vandetanib alone or a combination of both. The tumour volume was followed and compared with that in untreated GOT2 mice. The radiation dose and the amount of vandetanib were chosen to give moderate effect as single treatment to enable detection of any additive or synergistic effects. RESULTS: We found that the largest reduction in tumour size over time was seen for the animals receiving a combination of both EBRT and vandetanib. Given as single-agent treatment, EBRT and vandetanib resulted in a reduction in tumour size or in tumour growth arrest. For example, at two weeks after start of treatment, the tumour volume was reduced by 64%, 52%, and 73% compared with the untreated control group, for the animals treated with single EBRT, single vandetanib, and the combination, respectively. CONCLUSIONS: The results indicate that an additive or even synergistic effect could be achieved when combining irradiation with vandetanib for treatment of patients with MTC. Further studies should be made evaluating the full potential of combining vandetanib with 177Lu-octreotate for treatment of MTC.
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| 32. |
- Sandblom, Viktor, 1987, et al.
(författare)
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Visualisering av osynliga risker: optimering av strålskydd för säkrare arbetsmiljö
- 2013
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Ingår i: Röntgenveckan 2013, 3-6 september 2013, Uppsala.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Joniserande strålning innebär en ökad risk för cancer och katarakt. Sänkning av gränsvärden och att fler grupper av personal exponeras för strålning, t ex i hybridsalar, kan leda till att fler hamnar i riskzonen. För att minska dessa risker har tekniker utvecklats som visar exponeringen av strålning i realtid, vilket ger helt nya möjligheter för optimering av strålskydd. Mot denna bakgrund initierades ett tvärvetenskapligt samarbete vid Göteborgs universitet, Det övergripande syftet med projektet är att bidra med kunskap om hur visualisering av joniserande strålning i realtid kan användas för att åstadkomma en säkrare arbetsmiljö. Vi undersöker a) om och i så fall för vilka procedurer visuell feedback kan minska personalens exponering för strålning, b) hur personalens agerande kan bidra till detta och c) hur personal förstår information om de registrerade stråldoserna och hur deras individuella erfarenheter kan tas tillvara för att förbättra arbetsmetoder. En pilotstudie av visualisering av doser i realtid under röntgenvägledda procedurer visade att en av tre kardiologer och de assisterande sjuksköterskorna som grupp uppvisade en statistiskt signifikant minskning av sina doser. En slutsats är att systemet för visualisering kan ha en positiv påverkan för optimering av strålskydd och bidra till minskade risker i arbete med joniserande strålning.
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| 33. |
- Sandblom, Viktor, 1987
(författare)
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Ögondoser – ett problem inom interventionen?
- 2012
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Ingår i: Röntgenveckan 2012, Göteborg..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I april 2011 sänkte Internationella strålskyddskommissionen (ICRP) sin rekommenderade dosgräns för ögats lins, för personal som arbetar med joniserande strålning, från 150 mSv/år till 20 mSv/år. Med anledning av detta utfördes en studie på Sahlgrenska Universitetssjukhuset under hösten 2011. Huvudsyftet med studien var att uppskatta linsdos till personal som arbetar med röntgenvägledda procedurer. Ett delsyfte var att undersöka huruvida en dosimeter som bars i brösthöjd utanpå blyförklädet kunde användas för att uppskatta linsdosen. Denna presentation går djupare in på studiens metod, resultat och slutsatser.
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| 34. |
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| 35. |
- Shubbar, Emman, 1974, et al.
(författare)
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The effect of timing and sequence of gemcitabine administration and radiation for the treatment of medullary thyroid carcinoma.
- 2018
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - 1619-7070 .- 1619-7089.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumour with sometimes high expression of somatostatin receptors. MTC originates from the thyroid C cell and occurs either sporadically (75%) or is caused by germline mutation of the RET proto-oncogene. At diagnosis, about 50% of the MTC patients have metastases, and low 10-year survival rate for metastatic disease has been reported, about 20%. We recently investigated the effect of gemcitabine, a nucleoside analogue, which inhibits DNA synthesis and repair, in combination with 177Lu-octreotate or external beam radiotherapy (EBRT) in a patient-derived MTC (GOT2) animal model and our results suggested additive and even synergistic cytotoxic effects. However, the ideal timing of gemcitabine administration with irradiation has not been studied. The aim of this study is 1) to investigate whether the time course and sequence between gemcitabine administration and irradiation is essential for achieving high anti-tumor effect, and 2) to study the molecular mechanisms involved in the interaction between gemcitabine and radiation in GOT2. EBRT was used instead of 177Lu-ocreotate to enable studies of timing. Materials and Methods: Balb/C-nu mice with GOT2 tumours were divided into groups with a similar mean tumor volume at the start of treatment. The mice were injected with 60 mg/kg gemcitabine, either 72h before (group 1), 0.25h before (group 2) or 72h after (group 3) irradiation with 3Gy. Tumor size was measured twice a week, using a digital caliper. Results: For all groups, tumor regression was observed during the first 11 days with a mean relative volume reduction related to the volume before treatment of 21%, 40% and 46% for groups 1, 2 and 3, respectively. A statistically significant difference was observed between group 1 and groups 2 or 3 (P=0.029 and 0.030, respectively). The lower tumour reduction in group 1 could be due to accumulation of cells in S-phase, which are relatively more resistant to radiation. The higher tumour volume reduction when gemcitabine was given concurrently with or after EBRT, suggests increased delivery of gemcitabine to the MTC tumours and/or enhanced effect of the combination. Conclusions: Our findings suggest that the combined effect of gemcitabine and EBRT is higher when gemcitabine is administrated simultaneously with or after EBRT. The optimal time schedule of the combined modalities is further investigated, together with translation of results to 177Lu-octreotate therapy.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Ståhl, Ingun, 1984, et al.
(författare)
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Feasibility study of intraoperative gamma probes for determining 177Lu-octreotate activity concentration in vivo
- 2014
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Ingår i: SWE-RAYS (Swedish Radiation Research Association for Young Scientists) 3e årliga workshop, Malmö..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION 177Lu-octreotate is a good alternative for treatment of neuroendocrine tumors, with primarily kidneys as limiting organs. The development of a new treatment method using 177Lu-octreotate for liver metastases is under progress at our institute. This treatment method requires accurate activity concentrations of 177Lu-octreotate in tumor and normal tissues in vivo during surgery. Intraoperative gamma probes are mainly used for radio-guided surgery, where diagnostic radiopharmaceuticals including e.g. 99mTc or 111In are frequently used. The aim of this study was to investigate the possibility of using an intraoperative gamma probe for determining 177Lu-octreotate activity concentration in vivo. METHODS The performance of two intraoperative gamma probes was evaluated by determining the range for linear response and the spatial resolution (FWHM) at different depths using different sources containing 177Lu. To illustrate clinical conditions and further explore the ability of the gamma probes to distinguish tumor from normal tissues, measurements using various phantoms were performed. Tumor phantoms, made of agarose gel spheres (5-20 mm diameter) contained a high activity concentration of 177Lu, and were placed in a gel background containing a lower activity concentration of 177Lu, simulating tumors in a normal tissue. RESULTS A linear response (within ±10 %) was found for activities in the range of 1-30 MBq. The spatial resolution (FWHM) increased with depth (0 to 80 mm) from about 10 to 70 mm. The tumor phantom measurements showed high ratios between count rates measured over the gel spheres and the background gel, which indicates a good ability to distinguish between tumor and normal tissue. CONCLUSION The results in the present study imply that an intraoperative gamma probe could be used for measurements of activity concentration of 177Lu-octreotate in tissues in vivo.
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