Versatile synthetic approach to new bifunctional chelating agents tailor made for labeling with the fac-[M(CO)3]+ core (M = Tc, 99mTc, Re):: synthesis, in vitro, and in vivo behavior of the model complex [M(APPA)(CO)3] (APPA = [(5-amino-pentyl)-pyridin-2-yl-methyl-amino]-acetic acid)

被引:42
作者
Stichelberger, A
Waibel, R
Dumas, C
Schubiger, PA
Schibli, R [1 ]
机构
[1] ETH, Ctr Radiopharmaceut Sci, CH-5232 Villigen, Switzerland
[2] Paul Scherrer Inst, CH-5232 Villigen, Switzerland
[3] Univ Zurich Hosp, CH-5232 Villigen, Switzerland
关键词
bifunctional chelating agent; technetium; rhenium; organometallic;
D O I
10.1016/S0969-8051(03)00032-5
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
A general synthetic approach for potent tridentate, bifunctional chelating agent (BFCA) for the [M(CO)(3)](+) fragment (M=Tc-99g, Tc-99m, and Re) has be en elaborated. The strategy allows the facile preparation of BFCA with a pendent amino or carboxylic acid functionality for coupling to peptides and proteins via formation of an amide bond. [(5-amino-pentyl)-pyridin-2-yl-methyl-amino]-acetic acid (APPA) and [pyridin-2-yl-methyl-amino]-diacetic acid (PADA) were synthesized according to this protocol. The BFCA were labeled with the [M(CO)(3)](+) fragment, which resulted in formation of uniform products with a ligand to metal ratio of 1:1. The complexes have been fully characterized by means of mass spectrometry, IR, and NMR (H-1, C-13, Tc-99) spectroscopy. Coordination of the tricarbonyl core with APPA and PADA was exclusively tridentate (via the acid function, the ternary amine, and the pyridine nitrogen). On the n.c.a. level the complexes were almost quantitatively formed (yield>90%) at ligand concentrations of 10+/-2 muM (PADA) or 50+/-4 muM (APPA) after 30 min at 70degreesC. Chromatographic behavior of the Tc-99m complexes is similar to that of the corresponding Tc-99/Re complexes suggesting the identical chemical structure. Pharmacokinetic experiments with the Tc-99m-APPA complex were performed in BALB/c mice and compared with previously published results of the Tc-99m-PADA complex. The Tc-99m-APPA complex revealed good clearance from the blood pool (0.29+/-0.03% ID after 24h p.i.) and a low uptake in the liver (2.41+/-0.14% ID/g), in the kidneys (2.81+/-0.12% ID/g) and other tissue and organs. (C) 2003 Elsevier Inc. All rights reserved.
引用
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页码:465 / 470
页数:6
相关论文
共 18 条
[1]   Synthesis and structures of technetium(I) and rhenium(I) tricarbonyl complexes with bis(diphenylthiophosphoryl)amide, {M(CO)3[(Ph2PS)2N](CH3CN)} (M = Tc, Re) [J].
Abram, U ;
Abram, S ;
Schibli, R ;
Alberto, R ;
Dilworth, JR .
POLYHEDRON, 1998, 17 (08) :1303-1309
[2]  
Aebischer N, 2000, ANGEW CHEM INT EDIT, V39, P254, DOI 10.1002/(SICI)1521-3773(20000103)39:1<254::AID-ANIE254>3.0.CO
[3]  
2-F
[4]   METAL-CARBONYL SYNTHESES .22. LOW-PRESSURE CARBONYLATION OF [MOCL(4)](-) AND [MO4](-) - THE TECHNETIUM(I) AND RHENIUM(I) COMPLEXES [NET(4)](2)[MCL(3)(CO)(3)] [J].
ALBERTO, R ;
SCHIBLI, R ;
EGLI, A ;
SCHUBIGER, PA ;
HERRMANN, WA ;
ARTUS, G ;
ABRAM, U ;
KADEN, TA .
JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1995, 493 (1-2) :119-127
[5]   Reactions with the technetium and rhenium carbonyl complexes (NEt(4))(2)[MX(3)(CO)(3)]. Synthesis and structure of [Tc(CN-Bu(T))(3)(CO)(3)](NO3) and (NEt(4))[Tc-2(mu-SCH2CH2OH)(3)(CO)(6)] [J].
Alberto, R ;
Schibli, R ;
Schubiger, PA ;
Abram, U ;
Kaden, TA .
POLYHEDRON, 1996, 15 (07) :1079-1089
[6]   A novel organometallic aqua complex of technetium for the labeling of biomolecules:: Synthesis of [99mTc(OH2)3(CO)3]+ from [99mTcO4]- in aqueous solution and its reaction with a bifunctional ligand [J].
Alberto, R ;
Schibli, R ;
Egli, A ;
Schubiger, AP ;
Abram, U ;
Kaden, TA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (31) :7987-7988
[7]   Synthesis and properties of boranocarbonate:: A convenient in situ CO source for the aqueous preparation of [99mTC(OH2)3(CO)3]+ [J].
Alberto, R ;
Ortner, K ;
Wheatley, N ;
Schibli, R ;
Schubiger, AP .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (13) :3135-3136
[8]   Bifunctional single amino acid chelates for labeling of biomolecules with the {Tc(CO)3}+ and {Re(CO)3}+ cores.: Crystal and molecular structures of [ReBr(CO)3(H2NCH2C5H4N)], [Re(CO)3{(C5H4NCH2)2NH}]Br, [Re(CO)3{(C5H4NCH2)2NCH2CO2H}]Br, [Re(CO)3{X(Y)NCH2CO2CH2CH3}]Br (X = Y=2-pyridylmethyl; X=2-pyridyimethyl, Y=2-(1-methylimidazolyl)methyl; X = Y=2-(1-methylimidazolyl)methyl), [ReBr(CO)3{(C5H4NCH2)NH(CH2C4H3S)}], and [Re(CO)3{(C5H4NCH2)N(CH2C4H3S)(CH2CO2)}] [J].
Banerjee, SR ;
Levadala, MK ;
Lazarova, N ;
Wei, LH ;
Valliant, JF ;
Stephenson, KA ;
Babich, JW ;
Maresca, KP ;
Zubieta, J .
INORGANIC CHEMISTRY, 2002, 41 (24) :6417-6425
[9]   N-(2-mercaptoethyl)picolylamine as a diaminomonothiolate ligand for the "fac-[Re(CO)3]+" core [J].
Kramer, DJ ;
Davison, A ;
Davis, WM ;
Jones, AG .
INORGANIC CHEMISTRY, 2002, 41 (24) :6181-6183
[10]   Structural models for [M(CO)3(H2O)3]+ (M = Tc, Re):: fully aqueous synthesis of technetium and rhenium tricarbonyl complexes of tripodal oxygen donor ligands [J].
Kramer, DJ ;
Davison, A ;
Jones, AG .
INORGANICA CHIMICA ACTA, 2001, 312 (1-2) :215-220