DOTA-TYR3-OCTREOTATE LABELLED WITH ~(177)Lu AND ~(131)I: A COMPARATIVE EVALUATION

摘要

The chemical structure of somatostatin receptor ligand 1,4,7,10-tetraazacyclodo-decane-N,N',N' ,N''' -tetraacetic acid-Tyr3-octreotate (DOTA-Tyr3-TATE), provides the means for radiolabelling with halogen, by electrophilic substitution, to the Tyr3 residue and with metal, by a coordination mechanism, to the DOTA chelator. In this study, the DOTA-Tyr3-TATE was radiolabelled with ~(177)Lu and ~(131)I of high radiochemical purity and specific activity. The in vitro study regarding the competitive and the saturation binding assays were performed using rat brain cortex membrane. The IC_(50) value was determined as 4.74nM for ~(nat)Lu-DOTA-Tyr3-TATE and the K_d value was 142.8pM for ~(177)Lu-DOTA-Tyr3-TATE. The biodistribution data of ~(177)Lu-DOTA-Tyr3-TATE and DOTA-~(131)I-Tyr3-TATE in HRS1 (hepato-colangiom carcinomas) tumour bearing rats, show that the ~(177)Lu-DOTA-Tyr3-TATE is more stable and has better uptake than DOTA-~(131)I-Tyr3-TATE. Furthermore, the competitive localization index of ~(177)Lu-DOTA-Tyr3-TATE is three times higher than that obtained for DOTA-~(131)I -Tyr3-TATE. The results of work based on comparative experiments suggest that ~(177)Lu-DOTA-Tyr3-TATE could be an effective targeted radiotherapy agent of SSTR tumours.