JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS J Label Compd Radiopharm 2003; 46: 175–186. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.656 Research Article Synthesis and properties of radiolabeled CPTA–oligonucleotides S. Wagner 1 , R. Eritja 2 , M. Zuhayra 1 , F. Oberdorfer 1 , A. Mohammed 3 , W. Mier 3 , U. Haberkorn 3 and M. Eisenhut 1, * 1 German Cancer Research Center, Heidelberg, Germany 2 EMBL Heidelberg, Germany 3 Department of Nuclear Medicine, University of Heidelberg, Germany Summary A solid phase technique for the preparation of antisense oligodeoxynucleotides (ODNs) is described featuring 5 0 -end conjugated 4-[(1,4,8,11-tetraazacyclotet- radec-1-yl)-methyl]benzoic acid (CPTA). Using Fmoc-protected CPTA–C6 amidite, CPTA was conjugated to ODNs at the end of an automated DNA synthesis. To illustrate successful conjugations, the CPTA–ODNs were labeled with 99m Tc using the stannous-chloride reduction method. The resulting 99m Tc complexes showed differences of stability between CPTA-conjugated and CPTA-unconjugated as well as 3 0 -protected and 3 0 -unprotected ODNs. Propane-1,3-diol 3 0 -modification enhanced efficiently the stability of 99m Tc labeled ODN against exonuclease degradation. Fmoc 3 CPTA-C6 amidite turned out to be a versatile ligand for radiometal complexation at the 5 0 -end. Copyright # 2002 John Wiley & Sons, Ltd. Key Words: oligonucleotides; CPTA; solid phase synthesis; 99m Tc Introduction Synthetic oligonucleotides have extensively been employed to suppress DNA transcription or RNA translation. 1 Thus, antisense oligonucleo- Copyright # 2003 John Wiley & Sons, Ltd. Received 13 April 2002 Revised 13 August 2002 Accepted 19 August 2002 *Correspondence to: M. Eisenhut, EO300, Abt. Radiochemie/Radiopharmakologie Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. E-mail: m.eisenhut@dkfz.de