The stability of the 105[Rh(16S4diol)Cl2]+ radiopharmaceutical precursor in solutions containing human plasma thiols
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105Rh[1,5,9,13-tetrathiacyclohexadecane-3,11-diol] is a promising drug precursor for targeted radiotherapy. Nevertheless, the axial position of chloride ions in the complex structure and their weak binding to rhodium centre, due to HSAB concept, make such a complex subject to modifying action of certain sulphuric ligands, like human plasma thiol antioxidants: glutathione and cysteine. Experiments were performed with both radioactive 105Rh and inactive rhodium. The complexation of rhodium with 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16S4diol) resulted in three distinct peaks seen on UV, radiometric and MS chromatograms. The substitution of chlorides was noted in over 80% of 105[Rh(16S4diol)Cl2]+ units after incubation with glutathione, and less than 10% of complex units after incubation with cysteine (24 h, 37 °C). Reaction of 105[Rh(16S4diol)Cl2]+ with 1,8-octandithiol and 1,9-nonandithiol resulted in disappearance of the complex peak and occurrence of two new peaks. Product of RhCl3 and 16S4diol reaction is a mixture of three distinct forms having different number of chlorine atoms. Our in vitro experiments suggest that the substitution of axial chlorides with glutathione and cysteine might also occur in vivo in human plasma. Glutathione shows higher reactivity than cysteine in replacement reaction. Axial positions in precursor might be effectively blocked by 1,8-octandithiol and 1,9-nonandithiol.
Keywords105Rh 1,5,9,13-Tetrathiacyclohexadecane-3,11-diol Rhodium complex Glutathione Radiopharmacy
This study was supported by grant No. N204 143 32/3547 from the Ministry of Science and Higher Education, Poland, and by the European Cooperation in Science and Technology Action BM0607, Contract No. 53/040/2009, Dec. 368/N-COST/2008/0. The authors would like to thank the Structural Research Laboratory (SRL) at the Department of Chemistry, Warsaw University, Poland for access to HPLC-MS/MS. The SRL was established with financial support from the European Regional Development Fund in the Sectoral Operational Programme “Improvement of the Competitiveness of Enterprises, years 2004–2005” project No. WPK 1/1.4.3./1/2004/72/72/165/2005/U.
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