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Development of a radiolabeled glucagon compound for imaging

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Języki publikacji
EN
Abstrakty
EN
In order to develop a possible Ga-labeled glucagon (GCG) compound for imaging studies, biosynthetic glucagon (GCG) was labeled with [67Ga]-gallium chloride after conjugation with freshly prepared diethylenetriaminepentaacetic acid dianhydride (ccDTPA). After solid phase purification of the radiolabeled hormone, high performance liquid chromatography (HPLC) and instant thin-layer chromatography (ITLC) showed a radiochemical purity around 95 per cent in optimized conditions (specific activity = 296–370 GBq/mM; labeling efficiency 85 per cent). Preliminary in vivo studies (IDźg–1 per cent) in male wild-type rats showed heart:muscle, liver:muscle, lung:muscle and stomach:muscle ratios to be 5.53, 2.9, 7.56, 3.69, 3.2 (in 5 min), respectively while after 2 h liver:blood, lung:blood and spleen:blood ratios were 14.21, 16.86 and 7.8, respectively. The data suggests 5 min post injection, the tracer is accumulated in GCGR rich tissues which is in agreement with biodistribution studies and reported GCG receptors (GCGRs). The results of the present study can possibly offer a candidate for non-invasive imaging of glucagon receptor related diseased and malignancies such as glucagonoma.
Słowa kluczowe
Czasopismo
Rocznik
Strony
219--224
Opis fizyczny
Bibliogr. 20 poz., rys.
Twórcy
autor
autor
  • Radiopharmaceutical Research and Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Postal code: 14395-836, Tehran, Iran, Tel.: +98 21 8822 1103, Fax: +98 21 8822 1105, ajalilian@nrcam.org
Bibliografia
  • 1. Bastl C, Finkelstein FO, Sherwin R, Hendler R, Felig P, Hayslett JP (1977) Renal extraction of glucagon in rats with normal and reduced renal function. Am J Physiol Renal Physiol 233:F67–F71
  • 2. Blache P, Kervran A, Le-Nguyen D et al. (1993) Endopeptidase from rat liver membranes, which generates miniglucagon from glucagon. Biol Chem 268;29:21748–21753
  • 3. Canivet B, Gorden P, Carpentier JL, Orci L, Freychet P (1981) Glucagon degradation in isolated rat hepatocytes: effect of ammonium chloride and chloroquine. Mol Cell Endocrinol 23;3:311–320
  • 4. Carone FA, Peterson DR, Flouret G (1982) Renal tubular processing of small peptide hormones. J Lab Clin Med 100;1:1–14
  • 5. Davies K, Conlon KC (2009) Neuroendocrine tumors of the pancreas. Review. Curr Gastroenterol Rep 11;2:119–127
  • 6. Demoliou-Mason C, Epand RM (1982) Identification of the glucagon receptor by covalent labeling with a radiolabeled photoreactive glucagon analogue. Biochemistry 21;9:1996–2004
  • 7. Hagopian WA, Tager HS (1984) Receptor binding and cell-mediated metabolism of [125I]monoiodo-glucagon by isolated canine hepatocytes. J Biol Chem 259;14:8986–8993
  • 8. Hnatowich DJ, Layne WW, Child RL (1983) Radioactive labeling of antibody: a simple and efficient method. Science 220:613–619
  • 9. Hoosein NM, Gurd RS (1984) Identification of glucagon receptors in rat brain. Proc Natl Acad Sci USA 81;14:4368–4372
  • 10. http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/
  • 11. Information for the physician glucagon for injection (rDNA origin) PA 2284 AMP, Description. Literature revised February 18, 2005, Eli Lilly and Company, Indianapolis, IN 46285, USA
  • 12. Jalilian AR, Mehdipour P, Akhlaghi M, Yousefnia H, Shafaii K (2009) Evaluation of a [67Ga]-thiosemicarbazone complex as tumor imaging agent. Sci Pharm 77:343–354
  • 13. Jalilian AR, Mirsadeghi L, Haji-Hosseini R (2007) Preparation and biodistribution of [67Ga]-DTPA-rituximab in normal rats. J Radioanal Nucl Chem 274:175–179
  • 14. Jalilian AR, Rowshanfarzad P, Shafaii K et al. (2005) Development of 111In-DTPA-human polyclonal antibody complex for long-term inflammation/infection detection. Nukleonika 50:91–96
  • 15. Marczenko Z (1976) Spectrophotometric determination of elements. John Wiley & Sons Inc, New York, pp 238–240
  • 16. Obi N, Katabami T, Obi R, Odanaka M, Sasano K, Tanaka Y (2009) Primary malignant hepatic glucagonoma: an autopsy case. Endocr J 56;5:715–719
  • 17. Okauchi Y, Nammo T, Iwahashi H et al. (2009) Glucagonoma diagnosed by arterial stimulation and venous sampling (ASVS). Intern Med 48;12:1025–1030
  • 18. Peterson DR, Green EA, Oparil S, Hjelle JT (1986) Transport and hydrolysis of glucagon in the proximal nephron. Am J Physiol 251(3 Pt 2):F460–F467
  • 19. Pinto Marín A, Hernández Agudo E, Feliú J, González Barón M (2009) Pancreatic glucagonoma presenting as a pulmonary mass. Clin Transl Oncol 11;1:60–62
  • 20.Righetti PG, Tudor G, Ek K (1981) Isoelectric points and molecular weights of proteins. J Chromatogr 220:115–194
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-article-BUJ7-0014-0036
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