Expression of somatostatin receptors 3, 4, and 5 in mouse kidney proximal tubules

Bates, Carlton M.; Kegg, Heather; Petrevski, Christina; Grady, Sandy

doi:10.1046/j.1523-1755.2003.00716.x

Cited by 27 publications

(21 citation statements)

References 26 publications

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“…The high kidney uptake of 177 Lu-octreotate in the present study can be explained by the fact that kidneys in mice are one of few non-NE organs besides the pancreas that express all five SSTR (45)(46)(47). Further, there is a difference in the expression pattern of SSTR between human and mice kidneys, which complicates the translation of uptake data and dosimetry between species.…”

Section: Discussionmentioning

confidence: 72%

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

et al. 2011

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Abstract.To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177 Lu-octreotate and 111 In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177 Lu-octreotate or 111 In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111 In-MG0. Animals were sacrificed 1-7 days after injection in the 177 Lu-octreotate study and 1 h after injection of 111 In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177 Lu were calculated. There was a specific tumor uptake of either 177 Lu-octreotate or 111 In-MG0. 177 Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177 Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.

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Section: Discussionmentioning

confidence: 72%

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

et al. 2011

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“…Particular peptides may also be taken up by ligand-specific receptors, such as somatostatin receptors (15). Abundant expression of all somatostatin receptor subtypes has been described in the human and murine kidney (16,17), and subtypes 3 and 4 were found in the rat kidney (18). Rolleman et al retrospectively studied 111 In-octreotide scans of patients who were scanned before and during treatment with unlabeled octreotide.…”

Section: Proximal Tubular Reabsorption and Processingmentioning

confidence: 99%

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Vegt¹,

Jong²,

Wetzels³

et al. 2010

J Nucl Med

257

251

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Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.

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“…The study showed expression of all five ssts in the brain and pituitary, whereas other investigated organs, e.g., lungs, liver, and pancreas, varied in their tissue sst expression. The mRNAs for all five ssts were also detected in mouse brain (Fehlmann et al 2000) and in the retina (Cristiani et al 2002), whereas only sst [3][4][5] were expressed in the kidney (Bates et al 2003). However, to elucidate the more exact cellular distribution of sst, immunohistochemical (IHC) investigations are needed.…”

mentioning

confidence: 99%

Expression and Distribution of Somatostatin Receptor Subtypes in the Pancreatic Islets of Mice and Rats

Ludvigsen

Olsson

Stridsberg³

et al. 2004

J Histochem Cytochem.

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S U M M A R Y Somatostatin acts on specific membrane receptors (sst [1][2][3][4][5] ) to inhibit exocrine and endocrine functions. The aim was to investigate the distribution of sst [1][2][3][4][5] in pancreatic islet cells in normal mice and rats. Pancreatic samples from five adult C57BL/6 mice and Sprague-Dawley rats were stained with antibodies against sst 1-5 and insulin, glucagon, somatostatin, or pancreatic polypeptide (PP). A quantitative analysis of the co-localization was performed. All ssts were expressed in the pancreatic islets and co-localized on islet cells to various extents. A majority of the ␤ -cells expressed sst 1-2 and sst 5 in mouse islets, while Յ 50% in the rat expressed sst [1][2][3][4][5] . The expression of sst 1-5 on ␣ -cells did not differ much among species, with sst 2 and sst 5 being highly expressed. About 70% of the ␦ -cells expressed sst 1-4 in the rat pancreas, whereas 50% of the islet cells expressed sst 1-5 in the mouse. Furthermore, 60% of the PP-cells expressed sst [1][2][3][4][5] in the mouse, while the rat islets had lower values. Co-expression with the four major islet hormones varies among species and sst subtypes. These similarities and differences are interesting and need further evaluation to elucidate their physiological role in islets.

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Expression of somatostatin receptors 3, 4, and 5 in mouse kidney proximal tubules

Abstract: Expression of SSTR3, SSTR4, and SSTR5 in mouse proximal tubules complements the expression of SSTR1 and SSTR2 in collecting ducts as seen in other species. Taken together, the kidney is one of few organs expressing all five somatostatin receptors outside of the nervous system and pancreas.

Cited by 27 publications

References 26 publications

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention

Expression and Distribution of Somatostatin Receptor Subtypes in the Pancreatic Islets of Mice and Rats

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