Radiological impact of naturally occurring radionuclides in bottled water

Consumption of bottled water is increasing year after year in Europe. Due to the local geology from where the water is extracted; bottled water could be enhanced with radionuclides. This study focuses on the activity concentrations of 210Po, 210Pb, 226Ra, 228Ra, 234U and 238U in bottled water available in the Swedish market, to assess the radiological impact to different age groups. The results showed that among the 26 brands studied, only three could exceed the threshold value for drinking water: 0.1 mSv/year. For two brands, the dose was mainly due to the activity concentrations of 238U and 234U being up to 714 and 1162 mBq/L, respectively. While for one brand, the dose was mainly due to the activity concentration of both 210Po and 210Pb being around 100 mBq/L. For the remainder brands, 228Ra was the main contributor to the committed effective dose

Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

AbstractIntroductionThe kidneys are one of the main dose limiting organs in 177Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from 177Lu-octreotate exposure.MethodsFemale Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140MBq 177Lu-octreotate. The animals were killed 24h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes.ResultsDistinct transcriptional responses were observed following 177Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex.ConclusionSpecific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues

177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition

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

Dosimetric analysis of 123I, 125I and 131I in thyroid follicle models

BACKGROUND: Radioiodine is routinely used or proposed for diagnostic and therapeutic purposes: (123)I, (125)I and (131)I for diagnostics and (125)I and (131)I for therapy. When radioiodine-labelled pharmaceuticals are administered to the body, radioiodide might be released into the circulation and taken up by the thyroid gland, which may then be an organ at risk. The aim of this study was to compare dosimetric properties for (123)I, (125)I and (131)I in previously developed thyroid models for man, rat and mouse. METHODS: Dosimetric calculations were performed using the Monte Carlo code MCNPX 2.6.0 and nuclear decay data from ICRP 107. Only the non-radiative transitions in the decays were considered. The S value was determined for the cell nuclei in species-specific thyroid follicle models for mouse, rat and man for different spatial distributions of radioiodine. RESULTS: For the species-specific single follicle models with radioiodine homogeneously within the follicle lumen, the highest S value came from (131)I, with the largest contribution from the β particles. When radioiodine was homogeneously distributed within the follicle cells or the follicle cell nucleus, the highest contribution originated from (125)I, about two times higher than (123)I, with the largest contribution from the Auger electrons. The mean absorbed dose calculated for our human thyroid multiple follicle model, assuming homogenous distribution of for (123)I, (125)I, or (131)I within the follicle lumens and follicle cells, was 9%, 18% and 4% higher, respectively, compared with the mean absorbed dose according to Medical Internal Radiation Dose (MIRD) formalism and nuclear decay data. When radioiodine was homogeneously distributed in the follicle lumens, our calculations gave up to 90% lower mean absorbed dose for (125)I compared to MIRD (20% lower for (123)I, and 2% lower for (131)I). CONCLUSIONS: This study clearly demonstrates the importance of using more detailed dosimetric methods and models than MIRD formalism for radioiodine, especially (123)I and (125)I, in the thyroid. For radioiodine homogeneously distributed in the follicle lumens our calculations for the human multiple follicle models gave up to 90% lower mean absorbed dose compared with MIRD formalism

Tumour size measurement in a mouse model using high resolution MRI

Background Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10−2–10−1 g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice. Methods 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm3, using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. Results Strong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 1603 μm3 to 2403 μm3 without affecting the results significantly, thus reducing acquisition time substantially. Conclusions 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session