Microdosimetric analysis of 211At in thyroid models for man, rat and mouse

Josefsson, Anders; Forssell-Aronsson, Eva

doi:10.1186/2191-219x-2-29

Cited by 9 publications

(12 citation statements)

References 31 publications

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“…However, these results are from animal models and a translation of this data to the human system must be performed with caution, for all three radionuclides, as the photon contribution may be higher in clinical situations. 22,23 Results from the absorbed dose calculations showed that the thyroid received the maximum mean absorbed dose per unit injected activity, for all three radionuclides (Tables 4 and 5). This was expected due to the high activity concentration (400%IA/g for 125 I -, 430%IA/g for 131 Iand 75%IA/g for 211 At).…”

Section: Discussionmentioning

confidence: 97%

Biodistribution and Dosimetry of Free ²¹¹At, ¹²⁵I⁻ and ¹³¹I⁻ in Rats

Spetz

Rudqvist

Forssell-Aronsson

2013

Cancer Biotherapy and Radiopharmaceuticals

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131I is widely used for therapy in the clinic and 125I and 131I, and increasingly 211At, are often used in experimental studies. It is important to know the biodistribution and dosimetry for these radionuclides to determine potential risk organs when using radiopharmaceuticals containing these radionuclides. The purpose of this study was to investigate the biodistribution of 125I-, 131I-, and free 211At in rats and to determine absorbed doses to various organs and tissues. Male Sprague Dawley rats were injected simultaneously with 0.1-0.3 MBq 125I- and 0.1-0.3 MBq 131I-, or 0.05-0.2 MBq 211At and sacrificed 1 hour to 7 days after injection. The activities and activity concentrations in organs and tissues were determined and mean absorbed doses were calculated. The biodistribution of 125I- was similar to that of 131I- but the biodistribution of free 211At was different compared to 125I- and 131I-. The activity concentration of radioiodine was higher compared with 211At in the thyroid and lower in all extrathyroidal tissues. The mean absorbed dose per unit injected activity was highest to the thyroid. 131I gave the highest absorbed dose to the thyroid, and 211At gave the highest absorbed dose to all other tissues studied.

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Section: Discussionmentioning

confidence: 97%

Biodistribution and Dosimetry of Free ²¹¹At, ¹²⁵I⁻ and ¹³¹I⁻ in Rats

Spetz

Rudqvist

Forssell-Aronsson

2013

Cancer Biotherapy and Radiopharmaceuticals

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“…The degree of homogeneity in cellular irradiation - i.e., the fraction of non-hit, single-hit, or multi-hit cells in a population - most likely influences the biological response of a given tissue. This response depends not only on the amount of administered activity and tissue-specific uptake and clearing rates but also on, e.g., organ morphology, tissue structure, and size and density of cells ([ 29 ], Josefsson A, Forssell-Aronsson E. Microdosimetric analysis of the radio halogens 123 I, 124 I, 125 I, 131 I and 211 At, Submitted). Non-homogeneous irradiation may result in non-linear response to absorbed dose on the tissue level and/or increased intensity of, e.g., non-targeted effects [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and time

et al. 2015

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BackgroundIn cancer radiotherapy, knowledge of normal tissue responses and toxicity risks is essential in order to deliver the highest possible absorbed dose to the tumor while maintaining normal tissue exposure at non-critical levels. However, few studies have investigated normal tissue responses in vivo after 211At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from 211At in normal mouse tissues.MethodsFemale BALB/c nude mice were intravenously injected with 1.7 kBq 211At and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver, lungs, and spleen and subjected to microarray analysis. Enriched biological processes were categorized after cellular function based on Gene Ontology terms.ResultsResponses were tissue-specific with regard to the number of significantly regulated transcripts and associated cellular function. Dose rate effects on transcript regulation were observed with both direct and inverse trends. In several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript regulation at all exposure conditions.ConclusionsThis study demonstrated tissue-specific transcriptional responses and distinct dose rate effects after 211At administration. Transcript regulation of individual genes, as well as cellular responses inferred from enriched transcript data, may serve as biomarkers in vivo. These findings expand the knowledge base on normal tissue responses and may help to evaluate and limit side effects of radionuclide therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0078-7) contains supplementary material, which is available to authorized users.

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“…Percentage of scored vs. filtered transcripts is described as very low , 3%, low 3%-9%, medium 10%-29%, high 30%-49%, and very high $ 50% and highlighted as very light blue, light blue, blue, dark blue, very dark blue, respectively. a mean absorbed dose of 1.2 Gy would correspond to a statistical mean value of 1 a-particle track per thyroid cell (28). Accordingly, absorbed doses of 50 and 500 mGy at 0.064 and 0.64 kBq of 211 At, respectively, would result in around 4% and 40% of single-hit cells in thyroid tissue (17).…”

Section: Discussionmentioning

confidence: 99%