| 121. |
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| 123. |
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| 124. |
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| 125. |
- Svensson, Johanna, et al.
(författare)
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Nephrotoxicity profiles and threshold dose values for [(177)Lu]-DOTATATE in nude mice.
- 2012
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Ingår i: Nuclear medicine and biology. - : Elsevier BV. - 0969-8051. ; 39:6, s. 756-762
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In peptide receptor radionuclide therapy for neuroendocrine tumors the main dose-limiting tissue is found in the kidneys because of tubular reabsorption and retention of radioactivity. The aim of this study was to quantify late effects in renal cortex of nude mice exposed to high amounts of [(177)Lu]-DOTA-Tyr(3)-octreotate ([(177)Lu]-DOTATATE), and to determine whether a threshold dose value exists for these findings. METHODS: Nude mice were exposed to 90, 120 or 150MBq of [(177)Lu]-DOTATATE. Renal toxicity was evaluated up to 6 months after injection. Blood samples were collected to examine renal functional markers, and after sacrifice at 6 months changes in renal morphology were explored. Tissue damage was estimated by quantifying the relative area of the different subunits in the renal cortex using point counting. Additional morphological signs of radiation damage were also noted. The absorbed doses to the kidneys were estimated by previously determined kidney pharmacokinetics and Monte Carlo simulations for different assumptions regarding the activity distribution. RESULTS: Increased serum creatinine and urea values indicated long-term renal toxicity. The tissue area occupied by proximal tubules decreased with increasing doses of [(177)Lu]-DOTATATE, whereas the other subunits in cortex slightly increased. The mean absorbed dose in the renal cortex for [(177)Lu]-DOTATATE was estimated to be 35-58Gy for the different groups of animals. A dose-response relationship was observed for proximal tubular damage, and a threshold dose value of 24Gy (BED 37Gy) was determined. CONCLUSIONS: Selective morphological changes in kidney cortex of nude mice were quantified and appeared in a dose dependent manner after injection of high amounts of [(177)Lu]-DOTATATE.
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| 126. |
- Tisell, Lars-Eric, 1931, et al.
(författare)
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Expression of somatostatin receptors in oncocytic (Hürthle cell) neoplasia of the thyroid.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:9-10, s. 1579-82
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Tidskriftsartikel (refereegranskat)abstract
- Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.
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| 127. |
- Tisell, Lars-Eric, 1931, et al.
(författare)
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Somatostatin receptor scintigraphy in medullary thyroid carcinoma.
- 1997
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Ingår i: The British journal of surgery. - 0007-1323. ; 84:4, s. 543-7
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Tidskriftsartikel (refereegranskat)abstract
- 111In-radiolabelled (DTPA-D-Phe1)-octreotide scintigraphy can be used to localize neuroendocrine tumours expressing somatostatin receptors (SSTRs). The aim of this paper was to analyse the importance of tumour volume and growth for the visualization by SSTR scintigraphy of metastases from medullary thyroid carcinoma (MTC).
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| 128. |
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| 129. |
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| 130. |
- Wikström, Ingela, et al.
(författare)
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Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2.
- 2006
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 43:9, s. 1316-1324
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Tidskriftsartikel (refereegranskat)abstract
- Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dmu protein, we introduced Bcl-2 into Dmu-transgenic, Rag2-/- mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43- B cells, an identical increase was also observed in Rag2-/- mice. Moreover, whereas in mu-transgenic Rag2-/-Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dmu-transgenic Rag2-/- Bcl-2+ mice compared to Rag2-/- Bcl-2+ mice, indicating that Dmu cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dmu-transgenic recombination competent mice, the Dmu induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dmu protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dmu is exposed to the outer cell surface.
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