Please use this identifier to cite or link to this item:
標題: 抑制腎臟對放射核種標幟體抑素衍生物的吸收
Inhibition of Renal Uptake of Radiolabelled Somatostatin Analogues
作者: 張偉政
Chang, Wei-Cheng
關鍵字: Somatostatin
出版社: 獸醫學系暨研究所
引用: 林武智。利用迴旋加速器研製醫用放射性同位素。核醫會訊7:10-12,2001。 Arnold R, Frank M. Control of growth in neuroendocrine gastro-enteropancreatic tumors. Digestion 57: 69-71, 1996. Arnold R, Frank M, Kajdan U. Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues. Digestion 55: 107-113, 1994. Barone R, Jamar F, Walrand S. Amino acids infusion for renal protection during radiolabelled peptide therapy: comparison between different infusion regimens. Eur. J Nucl Med 27: 976, 2000. Barone R, Pauwels S, de Camps J, Krenning EP, Kvols LK, Smith MC, Bouterfa H, Devuyst O, Jamar F. Metabolic effects of amino acid solutions infused for renal protection during therapy with radiolabelled somatostatin analogues. Nephrol Dial Transplant 19: 2275-2281, 2004. Bauer W, Briner U, Doepfner W, Haller R Huguenin R, Marbach P, Petcher TJ, Pless J. A very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 31: 1133-1140, 1982. Baus M, Medjugorac-Popovski M, Brown D. In colchicine-treated rats, cellular distribution of AQP-1 in convoluted and straight proximal tubule segments is differently affected. Pflugers Arch 439:321-330, 2000. Behr TM, Becker WS, Sharkey RM, Juweid ME, Dunn RM, Bair HJ, Wolf FG, Goldenberg DM. Reduction of renal uptake of monoclonal antibody fragments by amino acid infusion. J Nucl Med 37: 829-833, 1996. Behr TM, Goldenberg DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med 25: 201-212, 1998. Bernard BF, Krenning EP, Breeman WAP, Rolleman EJ, Bakker WH, Visser TJ, Macke H, de Jong M. D-Lysing reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med 38: 1929-1933, 1997. Bravo EL. Pheochromocytoma. Cardiology Reviews 10: 44-50, 2002. Bruns C, Raulf F, Hoyer D, Schloos J, Lubbert H, Weckbecker G. Binding properties of somatostatin receptor subtypes. Metabolism 45: 17-20, 1996. Bruns C, Weckbecker G, Raulf F. Molecular pharmacology of somatostatin -receptor subtypes. Ann NY Acad Sci 733: 138-146, 1994. Burch HB, Choi S, Dence CN, Alvey TR, Cole BR, Lowry OH. Metabolic effects of large fructose loads in different parts of the rat nephron. J Biol Chem 255: 8239-8244, 1980. Camera L, Kinuya S, Garmestani K, Wu C, Brechbiel MW, Pai LH, McMurry TJ, Gansow OA, Pastan I, Paik CH, Carrasquillo JA. Evaluation of the serum stability and in vivo biodistribution of CHX-DTPA and other ligands for yttrium labeling of monoclonal antibodies. J Nucl Med 35: 882-889, 1994. Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G. Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Virchows Archives 425: 547-560, 1995. Caplin ME, Buscombe JR, Hilson AJ, Jones AL, Watkinson AF, Burroughs AK. Carcinoid tumor. Lancet 352: 799-805, 1998. Chinol M, Paganelli G, Sudati F, Meares C, Fazio F. Biodistribution in tumor-bearing mice of two 90Y-labelled biotins using three-step tumor targeting. Nucl Med Commun 18: 176-182, 1997. Christensen EI, Nielsen S. Structural and functional features of protein handling in the kidney proximal tubule. Semin Nephrol 11: 414-439, 1991. de Herder WW, Hofland LJ, van der Lely AJ, Lamberts SWJ. Somatostatin receptors in gastroenteropancreatic neuroendocrine tumors. Endocrine-Related Cancer 10: 451-458, 2003. de Jong M, Krenning E. New advances in peptide receptor radionuclide therapy. J Nucl Med 43: 617-620, 2002. de Jong M, Kwekkeboom D, Valkema R, Krenning EP. Radiolabelled peptides for tumor therapy: current status and future directions. Eur J Nucl Med and Mol Imaging 30: 463-469, 2003. de Jong M, Rolleman EJ, Bernard BF, Visser TJ, Bakker WH, Breeman WAP, Krenning EP. Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo. J Nucl Med 37: 1388-1392, 1996. Deshpande SV, DeNardo SJ, Kubis DL, Moi MK, McCall MJ, DeNardo GL, Meares CF. Yttrium-90-labeled antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent. J Nucl Med 31: 473-479, 1990. Dik K, Eric PK, Marion de J. Peptide receptor imaging and therapy. J Nucl Med 41: 1704-1713, 2000. Dik JK, Peter PK, Willem HB, Helmut RM, Eric PK. Comparison of 111In-DOTA-Tyr3 Octreotide and 111In-DTPA-Octreotide in the same patients: Biodistribution, Kinetics, Organ and Tumor Uptake. J Nucl Med 40: 762-767, 1999. Duncan JR, Welch MJ. Intracellular metabolism of indium-111-DTPA-labeled receptor targeted proteins. J Nucl Med 34: 1728-1738, 1993. Elkjaer ML, Birn H, Agre P, Christensen EI, Nielsen S. Effects of microtubule disruption on endocytosis, membrane recycling and polarized distribution of Aquaporin-1 and gp330 in proximal tubule cells. Eur J Cell Biol 67: 57-72, 1995. Eriksson B, Bergstrom M, Orlefors H, Sundin A, Oberg K, Langstrom B. Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. Quart J Nucl Med 44: 68-76, 2000. Faiss S, Scherubl H, Riecken EO, Wiedenmann B. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system. Recent Results in Cancer Research 142: 193-207, 1996. Froidevaux S, Eberle AN, Christe M, Sumanovski L, Heppeler A, Schmitt JS, Eisenwiener K, Beglinger C, Macke HR. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model. Int J Cancer 98: 930-937, 2002. Froidevaux S, Heppeler A, Eberle AN, Meier AM, Hausler M, Beglinger C, Behe M, Powell P, Macke HR. Preclinical comparison in AR4-2J tumor-bearing mice of four radiolabeled 1, 4, 7, 10 - tetraazacyclododecane - 1, 4, 7, 10 - tetraacetic acid - somatostatin analogs for tumor diagnosis and internal radiotherapy. Endocrinology 141: 3304-3312, 2000. Gibril F, Reynolds JC, Doppman JL, Chen CC, Venzon DJ, Termanini B, Weber C, Stewart CA, Jensen RT. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. Ann Intern Med 125: 26-34, 1996. Giuffrida D, Gharib H. Current diagnosis and management of medullary thyroid carcinoma. Annals of Oncology 9: 695-701, 1998. Guiellemin R. Peptides in the brain: the new endocrinology of the neurons. Science 202: 390-402, 1978. Hammond PJ, Wade AF, Gwillian ME, Peters AM, Myers MJ, Gilbey SG, Bloom SR, Calam J. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue. Br J Cancer 67: 1437-1439, 1993. Harrison HE, Harrison HC, Experimental production of renal glycosuria, phosphaturia and aminoaciduria by injection of maleic acid. Science 120: 606-608, 1954. Hellman B, Lernmark A. Inhibition of the in vitro secretion of insulin by an extract of pancreatic alpha-1 cells. Endocrinology 84: 1484-1488, 1969. Hellman P, Ladjevardi S, Skogseid B, Akerstrom G, Elvin A. Radiofrequency tissue ablation using cooled tip for liver metastases of endocrine tumors. World Journal of Surgery 26: 1052-1056, 2002. Hofland LJ, Visser-Wisselaar HA, Lamberts SW. Somatostatin analogs: clinical application in relation to human somatostatin receptor subtypes. Biochemical Pharmacology 50: 287-297, 1995. Hoyer D, Lubbert H, Bruns C. Molecular pharmacology of somatostatin receptors. Naunyn Schmiedeberg’s Archives of Pharmacology 350: 441-453, 1994. Isidori AM, Kaltsas G, Frajese V, Kola B, Whitelocke RA, Plowman PN. Ocular metastases secondary to carcinoid tumors: the utility of imaging with [123I]meta-iodobenzylguanidine and [111In]DTPA pentetreotide. Journal of Clinical Endocrinology and Metabolism 87: 1627-1633, 2002. James RD, Mary TS, Herman PW, Carolyn J, Anderson. Indium-111- Diethylenetriaminepentaacetic Acid -Octreotide is delivered in vivo to pancreatic, tumor cell, renal, and hepatocyte lysosomes. Cancer research 57: 659-671, 1997. Kaltsas GA, Mukherjee JJ, Grossman AB. The value of radiolabelled MIBG and octreotide in the diagnosis and management of neuroendocrine tumors. Annals of Oncology 12: S47-S50, 2001a. Kaltsas G, Mukherjee JJ, Plowman PN, Grossman AB. The role of chemotherapy in the nonsurgical management of malignant neuroendocrine tumors. Clinical Endocrinology 55: 575-587, 2001b. Kaltsas G, Rockall A, Papadogias D, Reznek R, Grossman AB. Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumors. European Journal of Endocrinology 151: 15-27, 2004. Kozak RW, Raubitschek A, Mirzadeh S, Brechbiel MW, Junghaus R, Gansow OA, Waldmann TA. Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-90 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity. Cancer Res 49: 2639-2644, 1989. Krenning EP, Bakker WH, Breeman WK, Koper JW, Kooij PP, Ausema L, Lameris JS, Reubi JC & Lamberts SW. Localisation of endocrine-related tumors with radioiodinated analogue of somatostatin. Lancet 1: 242-244, 1989. Krenning EP, Bakker WH, Kooij PP. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 33: 652-658, 1992. Krenning EP, Kooij PPM, Bakker WH, Breeman WAP, Postema PTE, Kwekkeboom DJ, Oei HY, De Jong M, Visser TJ, Reijs AEM, Lamberts SWJ. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPAD-Phe1]- Octreotide: a case history. Ann NY Acad Sci 733: 496-506, 1994. Krenning EP, Kooij PPM, Pauwels S, Breeman WAP, Postema PTE, Herder WWD, Valkema R, Kwekkeboom DJ. Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion 57: 57-61, 1996. Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman W, Kooij PPM, Oei HY, Hagen MV, Postema PTE, De Jong M, Reubi JC, Visser TJ, Reijs AEM, Hofland LJ, Koper JW, Lamberts SWJ. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 100 patients. Eur J Nucl Med 20: 716-731, 1993. Krenning EP, Kwekkeboom DJ, Pauwels S, Kvols LK, Reubi JC. Somatostatin receptor scintigraphy. Freeman M (ed) Nuclear Medicine Annual, 1-50, 1995. Kruhlich L, Dhariwal A, McCann S. Stimulatory and inhibitory effects of purified hypothalamic extracts on growth hormone release form rat pituitary in vitro. Endocrinology 83: 783-790, 1968. Kwekkeboom DJ, Kooij PP, Bakker WH, Macke HR, Krenning EP. Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the sam patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med 40: 762-767, 1999. Lamberts SW, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. The new England Journal of medicine 323: 1246-1249, 1990a. Lamberts SW, Bakker WH, Reubi JC, Krenning EP. Somatostatin receptor imaging in vivo localization of tumors with a radiolabeled somatostatin analog. Journal of Steroid Biochemistry and Molecular Biology 37: 1079-1082, 1990b. Lamberts SW, Krenning EP, Reubi JC. The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocrine Reviews 12: 450-482, 1991. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. New England Journal of Medicine 334: 246-254, 1996. Li WP, Lewis JS, Kim J, Bugaj JE, Johnson MA, Erion JL, Anderson CJ. DOTA-D-Tyr1-Octreotate: a somatostatin analogue for labeling with metal and halogen radionuclides for cancer imaging and therapy. Bioconjugate Chem 13: 721-728, 2002. Marcus H, Jochen S, Peter H, Jorg K, Dirk WB, Josef D, Helmut RM, Michael H, Jurgen D, Uwe H. PET imaging of Somatostatin Receptors using [68GA]DOTA-D-Phe1-Tyr3-Octreotide: First Results in Patients with Meningiomas. Journal Nuclear Medicine 42: 1053-1056, 2001. Marion J, Roelf V, Francois J, Larry K, Dik J, Wout AP, Willem HB, Chuck S, Stanislas P, Eric PK. Somatostatin receptor-targeted radionuclide therapy of tumors: Preclinical and Clinical Findings. Seminars in Nuclear Medicine 32: 133-140, 2002. Marshansky V, Bourgoin S, Londono I, Bendayan M, Maranda B, Vinay P. Receptor-mediated endocytosis in kidney proximal tubules: recent advances and hypothesis. Electrophoresis 18: 2661-2676, 1997. McCarthy KE, Woltering EA, Espenan GD, Cronin M, Maloney TJ, Anthony LB. In situ radiotherapy with 111In-pentetreotide: initial observations and future directions. Cancer J Sci Am 4(2): 94-102, 1998. Mogensen CE, Solling K. Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest 37: 477-486, 1977. Nielsen S. Endocytosis in proximal tubule cells involves a two-phase membranerecycling pathway. Am J Physiol 264: C823-C835, 1993. Oberg K. Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Current Opinion in Oncology 14: 38-45, 2002. Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, Maecke HR, Muller J. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 26: 1439-1447, 1999. Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, Heppeler A, Mueller-Brand J, Maecke HR. DOTATOC: a powerful new tool for receptor - mediated radionuclide therapy. Eur J Nucl Med 24: 791-795, 1997. Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 351: 417-418, 1998. Patel YC, Greenwood M, Kent G, Panetta R, Srikant CB. Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochemical and Biophysical Research Communications 192: 288-294, 1993. Patel YC. Molecular pharmacology of somatostatin receptor subtypes. Journal of Endocrinological Investigation 20: 348-367, 1997. Patel YC. Somatostatin and its receptor family. Frontiers in Neuroendocrinology 20: 157-198, 1999. Patel YC, Srikant CB. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hSSTR1-5). Endocrinology 135: 2814-2817, 1994. Pimm MV, Gribben SJ. Prevention of renal tubule reabsorption of radiometal (indium-111)-labeled Fab fragment of a monoclonal antibody in mice by systemic administration of lysine. Eur J Nucl Med 21: 663-665, 1994. Quadri SM, Shao Y, Blum JE, Leichner PK, Williams JR, Vriesendorp HM. Preclinical evaluation of intravenously administered 111In- and 90Y-labeled B72.3 immunoconjugate (GYC-DTPA) in beagle dogs. Nucl Med Biol 20: 559-570, 1993. Reisine T, Bell GI. Molecular biology of somatostatin receptors. Endocr Rev 16: 427-442, 1995. Reichlin S. Somatostatin. New England Journal of Medicine 309: 1495-1501, 1983a. Reichlin S. Somatostatin (secone of two parts). New England Journal of Medicine 309: 1556-1563, 1983b. Reubi JC, Krenning E, Lamberts SW, Kvols L. Somatostatin receptors in malignant tissues. Journal of Steroid Biochemistry and Molecular Biology 37: 1073-1077, 1990. Reubi JC, Laissue J, Krenning E, Lamberts SW. Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. Journal of Steroid Biochemistry and Molecular Biology 43: 27-35, 1992. Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A. Schmitt JS, Macke HR. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 27(3): 273-282, 2000. Ricke J, Klose KJ, Mignon M, Oberg K, Wiedenmann B. Standardisation of imaging in neuroendocrine tumors: results of a European delphi process. European Journal of Radiology 37: 8-17, 2001. Rolleman EJ, Krenning EP, Van Gameren A, Bernard BF, De Jong M. Uptake of [111In-DTPA0]octreotide in the rat kidney is inhibited by colchicine and not by fructose. J Nucl Med 45(4): 709-713, 2004. Rolleman EJ, Valkema R, de Jong M, Kooij PPM, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med 30: 9-15, 2003. Rosewicz S, Vogt D, Harth N, Grund C, Franke WW, Ruppert S, Schweitzer E, Riecken EO, Wiedenmann B. An amphicrine pancreatic cell line: AR42J cells co mbine exocrine and neuroendocrine properties. Eur J Cell Biol 59(1): 80-91, 1992. Rowlinson G, Snook D, Stewart S, Epenetos AA. Intravenous EDTA to reduce bone uptake of 90Y following 90Y-labelled antibody administration. Br J Cancer 59: 322, 1989. Sartori S, Nielsen I, Pennacchio G. Hyperkalaemia during infusion of hyperosmolar amino acid solutions enriched with branched chain amino acids. Recent Prog Med 82: 275-227, 1991. Schally AV. Oncological applications of somatostatin analogues. Cancer Research 48: 6977-6985, 1988. Shimon I, Taylor JE, Dong JZ. Somatostatin receptor subtype specificity in human fetal pituitary culture. J Clin Invest 99: 789-798, 1997. Shulkes A. Somatostatin: physiology and clinical applications. Balliere’s Clin Endocrinol Metab 8: 215-236, 1994. Skogseid B. Nonsurgical treatment of advanced malignant neuroendocrine pancreatic tumors and midgut carcinoids. World Journal of Surgery 25: 700–703, 2001. Slooter GD, Mearadji A, Breeman WA. Somatostatin receptor imaging, therapy and new strangies in patients with neuroendocrine tumors. Breast Journal Surgery 88: 31-40, 2001. Solcia E, Kloppel G, Sobin LH. Histological Typing of Endocrine Tumors, ed 2, pp 38–74. Springer Verlag, Berlin & Heidelberg, World Health Organisation, 2000. Stolz B, Smith-Jones P, Albert R, Tolcsvai L, Briner U, Ruser G, Ma¨cke H, Weckbecker G, Bruns C. Somatostatin analogues for somatostatinreceptor - mediated radiotherapy of cancer. Digestion 57: 17-21, 1996. Takano M, Nakanishi N, Kitahara Y, Sasaki Y, Murakami T, Nagai J. Cisplatininduced inhibition of receptor-mediated endocytosis of protein in the kidney. Kidney Int 62: 1707-1717, 2002. Taylor JE, Theveniau MA, Bashirzadeh R, Reisine T, Eden PA. Detection of somatostatin receptor subtype 2 (SSTR2) in established tumors and tumor cell lines: evidence for SSTR2 heterogeneity. Peptides 15: 1229-1236, 1994. Vanetti M, Kouba M, Wang X, Vogt G, Hollt V. Cloning and expression of a novel mouse somatostatin receptor (SSTR2B). FEBS Letters 311: 290-294, 1992. Vikic-Topic S, Raisch KP, Kvols LK, Vuk-Pavlovic S. Expression of somatostatin receptor subtypes in breast carcinoma, carcinoid tumor, and renal cell carcinoma. Journal of Clinical Endocrinology and Metabolism 80: 2974-2979, 1995. Virgolini I, Traub T, Novotny C, Leimer M, Fuger B, Li SR, Patri P, Pangerl T, Angelberger P, Raderer M, Burggasser G, Andreae F, Kurtaran A, Dudczak R. Exprience with indium-111 and yttrium-90-labeled somatostatin analogs. Current Pharmaceutical Design 8: 1781-807, 2002. Wall DA, Maak T. Endocytic uptake, transport and catabolism of proteins by epithelial cells. Am J Physiol 248: C12-C20, 1985. Weiner RE & Thakur ML. Radiolabeled peptides in the diagnosis and therapy of oncological diseases. Applied Radiation and Isotopes 57: 749-763, 2002. Worthen HG. Renal toxicity of maleic acid in the rat. Lab Invest 12: 791-801, 1963.
摘要: 神經內分泌腫瘤會表現具有高親合性的體抑素接受器,因此能夠利用放射核種標幟體抑素衍生物來進行閃爍造影技術而應用於這類腫瘤的診斷及治療。然而,腎臟會高度吸收放射核種所標幟的物質導致腎臟產生放射性毒性;這是因為經放射核種標幟的胜肽會經由絲球體濾過且有效的被近腎小管上皮細胞藉由飽飲作用攝入細胞內所引起的傷害。本研究我們嘗試利用各種正電胺基酸溶液和其他的物質來評估其抑制腎臟重吸收放射活性的能力及其安全性。方法:公的SD大鼠(200-250克),事先給予阻斷重吸收的處置,再由大鼠尾靜脈給予注射111In-DOTATOC。於注射後24小時,將大鼠犧牲,採取大鼠的數個器官並測量其放射活性。結果:改變尿液的pH值不能降低腎臟對111In-DOTATOC的吸收。而給予lysine (400 mg/kg)能夠產生超過40%抑制腎臟吸收放射活性的效果,但是它可能會造成高血鉀和代謝作用的改變。在合併給予arginine和histidine也能夠產生超過40%的抑制效果而且其造成的副作用較單獨給予lysine小。Maleate (400 mg/kg)是非常有效地能夠抑制超過50%的重吸收作用。另外,我們嘗試於注射111In-DOTATOC的前5小時分別給予colchicines (1 mg/kg)、vincristine (0.1 mg/kg)、noscapine (100 mg/kg)及nocodazole (1 mg/kg),發現能夠有意義的降低腎臟的重吸收(分別能降低31%、26%、41%及46%)。此外,合併給予正電胺基酸、ATP阻斷劑及Microtubule抑制劑的灌流有顯著抑制腎臟吸收放射活性的效果。結論:這些物質的給予能有效地降低腎臟的放射活性,以致於能夠給予較高劑量的放射核種標幟體抑素的衍生物,來進行閃爍造影的檢查及胜肽接受器放射核種的治療。
Neuroendocine tumors express high affinity somatostatin receptors that enable scintigraphic imaging using radiolabelled somatostatin analogues for application of tumors diagnosis and therapy. However, the high renal uptake of the radiolabelled compounds may lead to renal radiation toxicity, because of the radiolabelled peptides are filtered by the glomerulus and effectively taken up in proximal tubule cells by endocytosis. The aim of this study was to investigate of various basic amino acid solutions and other compounds in order to assess their safety and their capacity to inhibit the renal uptake of 111In-DOTATOC. Male Spraque-Dawley rats (200-250 g), in the presence of reuptake blocker, were injected with 111In-DOTATOC. At 24 hours after injection, rats were sacrificed and organs were isolated and counted for radioactivity. Our data show that changing the pH value of the urine did not reduced kidney uptake of 111In-DOTATOC. Lysine (400 mg/kg) were resulted in more than 40% inhibition of kidney uptake, but it may induce hyperkalacmia and metabolic changes. Combination of arginine and histidine were also resulted more than 40% inhibition, nevertheless it have less side effect than lysine. Maleate (400 mg/kg) were more effective to reduce renal uptake about over 50%. Further, coinjection of colchicines (1 mg/kg), vincristine (0.1 mg/kg), noscapine (100 mg/kg), nocodazole (1 mg/kg) 5 hours before injection of 111In-DOTATOC were significantly reduced kidney uptake (respective inhibitions of 31%, 26%, 41% and 46%). Besides, there is a notable inhibition of renal uptake by combining basic amino acids, ATP blockers, and microtubule inhibitors. Administration of these compounds effectively reduce kidney radioactivity in order to allow the administration of higher doses of radiolabelled somatostatin analogues for scintigraphy and peptide receptor radionuclide therapy.
其他識別: U0005-2901200705031500
Appears in Collections:獸醫學系所



Show full item record
TAIR Related Article

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.