Evaluation of two chelators for labelling a PNA monomer with the fac-[ 99mTc(CO) 3] + moiety

Abstract

A PNA monomer containing thymine as nucleobase ( 1) was synthesized, characterized and coupled to the pyrazolyl containing ligand 3,5-Me 2pz(CH 2) 2N((CH 2) 3COOH)(CH 2) 2NHBoc ( 2) and to a modified cysteine S-(carboxymethyl-pentafluorphenyl)- N-[(trifluor)carbonyl]- l-cysteine methyl ester ( 3) yielding the bifunctional chelators 6 and 7, respectively. Reactions of 6 and 7 with the Re(I) tricarbonyl starting material [Re(CO) 3(H 2O) 3]Br afforded the complexes fac-[Re(CO) 3(κ 3- 6)] + ( 8) and fac-[Re(CO) 3(κ 3- 7)] ( 9), respectively. The identity of 8 and 9 has been established based on IR spectroscopy, elemental analysis, ESI-MS spectrometry and HPLC. The multinuclear NMR spectroscopy ( 1H, 13C, g-COSY, g-HSQC) has also been very informative in the case of complex 8, showing the presence of rotamers in solution. For 9 the NMR spectrum was too complex due to the presence of rotamers and diastereoisomers. The radioactive congeners of complexes 8 and 9, fac-[ 99mTc(CO) 3(κ 3- 6)] + ( 8a) and fac-[ 99mTc(CO) 3(κ 3- 7)] ( 9a), have been prepared by reacting the precursor fac-[ 99mTc(CO) 3(H 2O) 3] + with the corresponding ligands being their identity established by comparing their HPLC chromatograms with the HPLC of the rhenium surrogates.