Henneken, H. (Corresponding author) ; Institut für Nuklearchemie (Jülich) ; Universität (Köln)

1995
Forschungszentrum Jülich

Report No.: Juel-3162

Abstract: 2-Nitroimidazole-derivatives are wideley used for the detection ofhypoxic cells in tumors, heart and brain. Wrth regard to the non-invasive detection ofhypoxic tissue with Single Photon Emission Tomography (SPET) four potential tracers have been synthesized. The following 2-nitroimidazole / amino acid conjugates were synthesized, labelled with radioiodine on the no carrier added (n.c.a.) level and biochemically evaluated: N-[2-(2-nitroimidazol-I-yl)-acetyl]-p-iod-D,L-phenylalanine methylester (I-1'2NI-Me), N-[2-(2-nitroimidazol-I-yl)-acetyl]-p-iod-D,L-pheny1a1anin.e buty1ami.de (!-P2NI-Ba), N-[2-(2-nitroimidazol-I-yl)-acetyl]-3-iod-es-methyl-D,L-tyrosine methylester (I-MTINI) N-[Z-(2-nitroimidazol-I-yl)-acetyl]-3-iod-0-methyl-o:-methyl-D,L-tyrosine methylester (I-MMT2NI). Moreover, the in vivo metabolite ofI-P2N1-Me, N-[Z-(Z-nitroimidazol-l-yl)-acetyl]-p-iod-D,Lphenylalanine (I-1'2NI-S), was synthesized as a standard and radioiodinated N.c.a. radioiodination ofthe phenylalanine derivatives I-1'2NI-Me and I-1'2NI-Ba was achieved in >90% radiochemical yield (RCY) via copper(I) assisted radio-iododebromination. The classical method using copper(II) in combination with reducing agents such as stannous sulfate in aqueous acidic medium for the in situ formation of copper(I) did not work, because the phenylalanine derivatives are prone to reduction and hydrolysis. The application ofMoerlein's reductant- and acid free method (Cu(I)CI in DMSO) resulted in low RCY. In order to obtain satisfactory RCY a new, milder copper(I)-system was developed. It consisted of CuzSO. as the metal salt andDMSO as the preferred reaction solvent. For the optimisation ofthis systemthe most important parameters like solvents, reaction temperature, precursor and couprous sulfute concentrations were examined. The best results for the radioiodination ofthe phenylalanine derivatives I-P2NI-Me and I-P2NI-Ba with the new labelling system were obtained with a copper(I) concentration of Z mM and the addition of equimolar amounts of citric acid or 2,5dihydroxyterephthalic acid at 140°C. After 3-4h at this temperature a RCY of >90% was obtained. Thus, compared to known labelling systems using copper(I) the new Cu,SOJDMSO system represents a mild and efficient system for the labelling of reduction and hydrolysis sensitive compounds. The reaction mechanism involving a complex-like transition state was also shown for this system

Keyword(s): labeled compound ; labeling ; iodine ; amino acid ; hypoxia

1. Nuklearchemie (INB-4)