A novel tetrabranched neurotensin(8-13) cyclam derivative: Synthesis, 64Cu-labeling and biological evaluation

被引:19
|
作者
Roehrich, Anika [1 ]
Bergmann, Ralf [1 ]
Kretzschmann, Anne [1 ]
Noll, Steffi [1 ]
Steinbach, Joerg [1 ]
Pietzsch, Jens [1 ]
Stephan, Holger [1 ]
机构
[1] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharm, D-01314 Dresden, Germany
关键词
Neurotensin receptor; Cyclam derivatives; Tetramer; Copper-64; Colorectal adenocarcinoma; Small animal positron emission tomography; TARGETED TUMOR-DIAGNOSIS; IN-VIVO EVALUATION; 1,4,8,11-TETRAAZACYCLOTETRADECANE CYCLAM; BRANCHED PEPTIDES; RADIOLABELED SOMATOSTATIN; ACTIVITY CU-64; RT-PCR; ANALOGS; COPPER(II); RECEPTORS;
D O I
10.1016/j.jinorgbio.2011.02.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
New macrocyclic 1,4,8,11-tetraazacyclotetradecane (cyclam) derivatives with 1, 2 and 4 neurotensin(8-13) units 4, 5 and 7 have been synthesized. Compounds 4 and 5 were prepared by the reaction of non-stabilized neurotensin(8-13) and cyclamtetrapropionic acid 2 using 1-ethyl-3-(3-dimethylaminocarbonyl)carbodiimide-hydrochloride and N-hydroxysulfosuccinimide. The tetrameric compound 7 was synthesized by Michael addition of neurotensin(8-13) acrylamide 6 and cyclam 1. The copper(II) complexation behavior of 4, 5 and 7 was investigated by UV/visible spectrophotometry and shows that the metal center resides inside the N4 chromophore with additional apical interactions established with pendant arms. The novel tetrabranched NT(8-13) cyclam 7 with nanomolar neurotensin receptor 1 binding affinity was efficiently radiolabeled with Cu-64 under mild conditions. Cu-64 subset of 7 showed slow transchelation in the presence of a large amount of cyclam as competing ligand, while it completely remains intact in the presence of EDTA. The in vivo behavior of Cu-64 subset of 7 was studied in rats and mice. The metabolic stability in rodent models was high with a half-life of intact Cu-64 subset of 7 in plasma of 34 min in rats and 60 min in the mice, respectively. The binding affinity was high enough to demonstrate in vivo binding of Cu-64 subset of 7 to NTR1 overexpressing HT-29 tumor xenotransplants in nude mice. Regarding elimination, Cu-64 subset of 7 showed a substantial renal and reticuloendothelial accumulation. On the other hand, metabolization of the compound in vivo with a resulting metabolite-postulated to be the Cu-64-cyclam-tetraarginine complex-also showed long retention in the circulating blood, preventing a better contrast of tumor imaging. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:821 / 832
页数:12
相关论文
共 20 条
  • [1] Synthesis and biological studies of novel neurotensin(8-13) mimetics
    Feng, HJ
    Zaidi, J
    Cusack, B
    Richelson, E
    BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (12) : 3849 - 3858
  • [2] Synthesis, Cu(II) complexation, 64Cu-labeling and biological evaluation of cross-bridged cyclam chelators with phosphonate pendant arms
    Ferdani, Riccardo
    Stigers, Dannon J.
    Fiamengo, Ashley L.
    Wei, Lihui
    Li, Barbara T. Y.
    Golen, James A.
    Rheingold, Arnold L.
    Weisman, Gary R.
    Wong, Edward H.
    Anderson, Carolyn J.
    DALTON TRANSACTIONS, 2012, 41 (07) : 1938 - 1950
  • [3] SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF NOVEL NEUROTENSIN(8-13) ANALOGUES
    Dzimbova, T.
    Stoeva, S.
    Tancheva, L.
    Georgieva, A.
    Kalfin, R.
    Pajpanova, T.
    JOURNAL OF PEPTIDE SCIENCE, 2014, 20 : S241 - S241
  • [4] Synthesis and evaluation of novel multimeric neurotensin(8-13) analogs
    Hultsch, Christina
    Pawelke, Beate
    Bergmann, Ralf
    Wuest, Frank
    BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (17) : 5913 - 5920
  • [5] Synthesis, Cu(II) complexation, 64Cu-labeling and biological evaluation of CB-TE1A1P
    Ferdani, Riccardo
    Guo, Yunjun
    Stigers, Dannon
    Fiamengo, Ashley L.
    Wei, Lihui
    Wong, Edward H.
    Weisman, Gary R.
    Anderson, Carolyn J.
    NUCLEAR MEDICINE AND BIOLOGY, 2010, 37 (06) : 690 - 690
  • [6] Neurotensin(8-13) analogue: radiolabeling and biological evaluation using different chelators
    Teodoro, Rodrigo
    Faintuch, Bluma Linkowski
    Fernandez Nunez, Eutimio Gustavo
    Queiroz, Rodrigo Guimaraes
    NUCLEAR MEDICINE AND BIOLOGY, 2011, 38 (01) : 113 - 120
  • [7] 64Cu-labeling and biological evaluation of sarcophagine-based peptide for beta cell imaging
    Yim, Cheng-Bin
    Mikkola, Kirsi
    Rajander, Johan
    Greguric, Ivan
    Elomaa, Viki-Veikko
    Ishizu, Tamiko
    Nuutila, Pirjo
    Solin, Olof
    JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2013, 56 : S68 - S68
  • [8] Design, synthesis and pharmacological evaluation of active pyrrole based, nonpeptidic analogues of neurotensin(8-13)
    Hong, F
    Zaidi, J
    Pang, YP
    Cusack, B
    Richelson, E
    JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1997, (20): : 2997 - 3003
  • [9] Data set describing the in vitro biological activity of JMV2009, a novel silylated neurotensin(8-13) analog
    Besserer-Offroy, Elie
    Tetreault, Pascal
    Brouillette, Rebecca L.
    Rene, Adeline
    Murza, Alexandre
    Fanelli, Roberto
    Kirby, Karyn
    Parent, Alexandre
    Dubuc, Isabelle
    Beaudet, Nicolas
    Cote, Jerome
    Longpre, Jean-Michel
    Martinez, Jean
    Cavelier, Florine
    Sarret, Philippe
    DATA IN BRIEF, 2020, 31
  • [10] Synthesis and evaluation of Tc-99m-tricarbonyl labeled glycine oligomers for radiolabeling of neurotensin(8-13)
    Jang, Beom-Su
    Lee, Joo-Sang
    Rho, Jong Kook
    Park, Sang Hyun
    JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2013, 56 : S411 - S411