PT  - JOURNAL ARTICLE
AU  - Hueting, Rebekka
AU  - Christlieb, Martin
AU  - Dilworth, Jon
AU  - Garcia Garayoa, Elisa
AU  - Gouverneur, Veronique
AU  - Jones, Michael
AU  - Maes, Veronique
AU  - Schibli, Roger
AU  - Sun, Xin
AU  - Tourwe, Dirk
TI  - Bis(thiosemicarbazones) as bifunctional chelators for the room-temperature 64-copper labeling of peptides and proteins
DP  - 2010 May 01
TA  - Journal of Nuclear Medicine
PG  - 1459--1459
VI  - 51
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/51/supplement_2/1459.short
4100  - http://jnm.snmjournals.org/content/51/supplement_2/1459.full
SO  - J Nucl Med2010 May 01; 51
AB  - 1459 Objectives Virtually all Cu-chelating systems to date require heating to achieve high radiochemical yields. We have developed a new series of bis(thiosemicarbazone) based Cu(II)-chelators bearing pendant COOH groups in order to develop a chelating system that labels at ambient temperature and pH for labeling sensitive systems. Methods The new bis(thiosemicarbazone) chelators bearing aliphatic and aromatic linkers were successfully synthesised and radiolabeled with 64-Cu and 99m-Tc. Two chelators were conjugated to stabilised bombesin and postlabeled with 64-Cu. Receptor binding studies, internalisation assays and preliminary biodistribution data was obtained using 64/67Cu-(ATSM)-BBS in nude mice with PC-3 tumour xenografts. Results The radiochemical yields for CuATSM-BBS-1 and CuATSM-BBS-2 at room temperature were 91 % and 85 % respectively, labeling at 75°C resulted in yields of 90-95 %. HPLC analysis after 24h showed that the complexes were stable in solution. EPR characterisation indicates rapid labeling and site specificity are maintained when conjugated to a biologically active molecule. Preliminary in vivo studies indicate good uptake with a tumour/muscle ratio of 9.6:1 at 1 h p.i. Significantly this value was reduced by about 52% during blocking studies. In addition, the same ligands could also be labeled with 99m-Tc in high radiochemical purity. Conclusions Initial in vitro and in vivo evaluations of these first generation bis(thiosemicarbazone) functionalised chelators show that they are in principle suitable for protein targeted PET imaging. 99m-Tc-labeling experiments show that these new ATSM derivatives are also promising for the SPECT labeling of proteins