Determination of Absorbed Dose to Blood, Kidneys, Testes and Thyroid in Mice Injected With 211At and Comparison of Testes Mass and Sperm Number in X-irradiated and 211At Treated Mice

Harrison, A.; Royle, Leanne

doi:10.1097/00004032-198402000-00013

Cited by 17 publications

(9 citation statements)

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“…Auger electrons have RBE values of 1.5-40 depending on the electron energy and the location of the radionuclide, because of the limited range of these particles (25). Likewise, reported RBE values for the a-particle emitter 211 At vary between 1.5 and 25 for different tissues, experimental conditions, and endpoints (26)(27)(28)(29)(30)(31)(32)(33). In the present study, the doseresponse curves presented in Figure 4 allow an estimation of RBE (at the absorbed dose levels required to reduce the relative 125 I transport by 1 natural log, 37%) for the stunning effect induced by 123 I, compared with 131 I, which was about 5 (estimated from Fig.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

Lundh

Lindencrona²,

Postgård³

et al. 2009

J Nucl Med

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Recent clinical and experimental data demonstrate that thyroid stunning is caused by previous irradiation and may influence the efficacy of 131 I radiation therapy of thyroid cancer and possibly hyperthyroidism. To avoid stunning, many clinics have exchanged 131 I for 123 I for pretherapeutic diagnostic imaging and dose planning. Furthermore, recent in vitro studies indicate that 131 I irradiation reduces iodide uptake by downregulating the expression of the sodium iodide symporter (NIS). The rationale for this study was therefore to study effects on iodide transport and NIS messenger RNA (mRNA) expression in thyrocytes exposed to both 123 I and 131 I in addition to some other potentially interesting radionuclides. Methods: Thyrotropin-stimulated thyroid cell monolayers were exposed to 0.5 Gy of 123 I, 131 I, 99m Tc, or 211 At, all being radionuclides transported via NIS, in the culture medium for 6 h, or to various absorbed doses of 123 I or 131 I for 48 h. NIS mRNA expression was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Results: Iodide transport and NIS mRNA expression were reduced by all radionuclides. At the same absorbed dose, iodide transport was reduced the most by 211 At, followed by 123 I and 99m Tc (equally potent), whereas 131 I was least effective. The onset of NIS downregulation was rapid (,1 d after irradiation) in cells exposed to 123 I or 211 At and was delayed in cells irradiated with 131 I or 99m Tc. Iodide transport and NIS expression were recovered only for 211 At. 123 I reduced the iodine transport and the NIS mRNA expression more efficiently than did 131 I at an equivalent absorbed dose, with a relative biological effectiveness of about 5. Conclusion: The stunning effect per unit absorbed dose is more severe for 123 I than for 131 I. Despite the lower absorbed dose per unit activity for 123 I than for 131 I, stunning by 123 I cannot be excluded in patients. The degree to which iodide transport capacity and NIS mRNA expression are reduced seems to be related to the biological effectiveness of the type of radiation delivering the absorbed dose to the target, with 211 At (which has the highest relative biological effectiveness) causing the highest degree of stunning per unit absorbed dose in the present study.

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Section: Discussionmentioning

confidence: 99%

Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

Lundh

Lindencrona²,

Postgård³

et al. 2009

J Nucl Med

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“…The biodistribution of 125 I -, 131 Iand free 211 At has been studied in mice. [8][9][10][11][12] The results demonstrate clear differences between the radionuclides and show a higher accumulation of 211 At compared to radioiodine in all organs and tissues except the thyroid. The difference in size between rats and mice makes organ sampling easier in rats, particularly for the smaller organs (such as thyroid which is one of the risk organs), which can be difficult to entirely excise alone in mice.…”

Section: Introductionmentioning

confidence: 99%

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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“…The mean weight of the thyroid gland for man is approximately 19 g (range 8 to 48 g) [30], for rat approximately 30 mg [31] and approximately 3 mg for mouse [12,17]. There is also a difference in follicle size between the species.…”

Section: Discussionmentioning

confidence: 99%

“…The cumulated activity equivalent to a mean absorbed dose to the thyroid of 1 Gy for the different species was calculated under the following assumptions: ϕ = 1, Δ = 6.8 MeV and m is 3 mg for mouse, 30 mg for rat and 19 g for man [12,17,30,31]. …”

Section: Methodsmentioning

confidence: 99%

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

Josefsson

Forssell-Aronsson

2012

EJNMMI Research

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BackgroundThe alpha particle emitter 211At is proposed for therapy of metastatic tumour disease. 211At is accumulated in the thyroid gland in a similar way as iodine. Dosimetric models of 211At in the thyroid are needed for radiation protection assessments for 1) patients receiving 211At-labelled pharmaceuticals where 211At may be released in vivo and 2) personnel working with 211At. Before clinical trials, preclinical studies are usually made in mice and rats. The aims of this study were to develop thyroid models for mouse, rat and man, and to compare microdosimetric properties between the models.MethodsA thyroid follicle model was constructed: a single layer of 6 to 10-μm thick follicle cells with centrally positioned 4 to 8 μm (diameter) spherical nuclei surrounded a 10 to 500 μm (diameter) spherical follicle lumen. Species-specific models were defined for mouse, rat and man. The source compartments for 211At were the follicle lumen, follicle cells and follicle cell nuclei. The target was the follicle cell nucleus. Simplified species-specific thyroid models were used to investigate the contribution from surrounding follicles. Monte Carlo simulations were performed using the general purpose radiation transport code MCNPX 2.6.0.ResultsWhen 211At was homogeneously distributed within the follicle lumen, the mean specific energies per decay, 〈z〉, to the follicle cell nucleus were 2.0, 1.1 and 0.17 mGy for mouse, rat and man, respectively. Corresponding values for the single-hit mean specific energy per decay, 〈z1〉, were 1.3, 0.61 and 0.37 Gy. Assuming a homogeneous 211At concentration in the follicle lumen, <0.5%, 7%, and 45% of the emitted alpha particles were fully stopped within the follicle lumen for the respective models.ConclusionsThe results clearly show the influence of the follicle size, alpha particle range and 211At location within the thyroid follicle on the dosimetric parameters. Appropriate thyroid models are required for translation of dosimetric parameters between species.

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Determination of Absorbed Dose to Blood, Kidneys, Testes and Thyroid in Mice Injected With 211At and Comparison of Testes Mass and Sperm Number in X-irradiated and 211At Treated Mice

Cited by 17 publications

References 2 publications

Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

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

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

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Determination of Absorbed Dose to Blood, Kidneys, Testes and Thyroid in Mice Injected With 211At and Comparison of Testes Mass and Sperm Number in X-irradiated and 211At Treated Mice

Cited by 17 publications

References 2 publications

Radiation-Induced Thyroid Stunning: Differential Effects of 123I, 131I, 99mTc, and 211At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

Radiation-Induced Thyroid Stunning: Differential Effects of 123I, 131I, 99mTc, and 211At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

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

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

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Product

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Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

Radiation-Induced Thyroid Stunning: Differential Effects of ¹²³I, ¹³¹I, ^99mTc, and ²¹¹At on Iodide Transport and NIS mRNA Expression in Cultured Thyroid Cells

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