In vitro and in vivo evaluation of 64Cu-Labeled DOTA-Linker-Bombesin(7-14) analogues containing different amino acid linker moieties

被引:98
作者
Parry, Jesse J. [1 ]
Kelly, Thomas S. [1 ]
Andrews, Rebecca [1 ]
Rogers, Buck E. [1 ]
机构
[1] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, Dept Radiat Oncol, St Louis, MO 63110 USA
关键词
D O I
10.1021/bc0603788
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The gastrin-releasing peptide receptor (GRPR) is overexpressed on a variety of tumor types and has been targeted with radiolabeled peptides for detection and therapy of these cancers. Analogues of the 14 amino acid bombesin (BN) peptide have been radiolabeled with both gamma- and positron-emitting radionuclides for detection of GRPR-expressing tumors. We have previously evaluated BN analogues radiolabeled with the positron-emitter, copper-64 (Cu-64), that contained various aliphatic linkers placed between the BN peptide and the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator. These studies showed that the analogues could be used for positron-emission tomographic (PET) imaging of GRPR-positive tumors in mice but clinical translation would be hindered by significant uptake in background tissues. Therefore, the purpose of this study was to determine if the use of amino acid linkers placed between the DOTA chelate and the BN peptide would reduce nontarget tissue uptake, while maintaining good prostate tumor uptake. The linkers studied utilized three amino acid combinations of glycine (G), serine (S), or glutamic acid (E). In vitro assays in PC-3 cells showed that the glutamic acid-containing linkers had poor binding and internalization, while the other analogues had IC50 values < 100 nM and good internalization. In vivo, these same analogues demonstrated tumor-specific uptake and good imaging characteristics that were comparable to, or better than the previously reported Cu-64-labeled DOTA-BN analogues. Overall, this study shows that BN analogues containing amino acid linkers can be used for the PET imaging of GRPR-expressing prostate cancer and that these linkers lead to lower background tissue uptake.
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页码:1110 / 1117
页数:8
相关论文
共 33 条
[1]   Pyrazolyl conjugates of bombesin:: a new tridentate ligand framework for the stabilization of fac-[M(CO)3]+ moiety [J].
Alves, Susana ;
Correia, Joao D. G. ;
Santos, Isabel ;
Veerendra, Bhadrasetty ;
Sieckman, Gary L. ;
Hoffman, Timothy J. ;
Rold, Tammy L. ;
Figueroa, Said Daibes ;
Retzloff, Lauren ;
McCrate, Joseph ;
Prasanphanich, Adam ;
Smith, Charles J. .
NUCLEAR MEDICINE AND BIOLOGY, 2006, 33 (05) :625-634
[2]   ISOLATION AND STRUCTURE OF BOMBESIN AND ALYTESIN, 2 ANALOGOUS ACTIVE PEPTIDES FROM SKIN OF EUROPEAN AMPHIBIANS BOMBINA AND ALYTES [J].
ANASTASI, A ;
ERSPAMER, V ;
BUCCI, M .
EXPERIENTIA, 1971, 27 (02) :166-&
[3]   Bombesin antagonists inhibit growth of MDA-MB-435 estrogen-independent breast cancers and decrease the expression of the ErbB-2/HER-2 oncoprotein and c-jun and c-fos oncogenes [J].
Bajo, AM ;
Schally, AV ;
Krupa, M ;
Hebert, F ;
Groot, K ;
Szepeshazi, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) :3836-3841
[4]   MOLECULAR-CLONING OF THE BOMBESIN GASTRIN-RELEASING PEPTIDE RECEPTOR FROM SWISS 3T3 CELLS [J].
BATTEY, JF ;
WAY, JM ;
CORJAY, MH ;
SHAPIRA, H ;
KUSANO, K ;
HARKINS, R ;
WU, JM ;
SLATTERY, T ;
MANN, E ;
FELDMAN, RI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (02) :395-399
[5]   Comparative in vivo stability of copper-64-labeled cross-bridged and conventional tetraazamacrocyclic complexes [J].
Boswell, CA ;
Sun, XK ;
Niu, WJ ;
Weisman, GR ;
Wong, EH ;
Rheingold, AL ;
Anderson, CJ .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (06) :1465-1474
[6]  
Breeman WAP, 2002, J NUCL MED, V43, P1650
[7]   Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations [J].
Buchholz, Stefan ;
Keller, Gunhild ;
Schally, Andrew V. ;
Halmos, Gabor ;
Hohla, Florian ;
Heinrich, Elmar ;
Koester, Frank ;
Baker, Benjamin ;
Engel, Joerg B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10403-10407
[8]  
Chen XY, 2004, J NUCL MED, V45, P1390
[9]   New 64Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr [J].
Di Bartolo, Nadine ;
Sargeson, Alan M. ;
Smith, Suzanne V. .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (17) :3350-3357
[10]  
FATHI Z, 1993, J BIOL CHEM, V268, P5979