DOTA-TATE alternative labellings with halogens and radiometals

摘要

DOTA-D-phe-cys-tyr-D-trp-lys-thr-cys-thr (DOTA-TATE), a somatostatin analog withrnhigh affinity for somatostatin receptors expressed in cancer of neuroendocrine origin, may bernlabelled with different beta emitting radionuclides for its use in targeted radiotherapy. In this studyrnthe labelling of DOTA-TATE with 125I, 131I and 177Lu and their biological properties wererninvestigated, with the aim of potential application as tumor seeking agents. Radiolabelling with 125I,rn131I and 177Lu, in vitro stability, biological behavior of radiolabelled peptides and biodistributionrnwere investigated, optimezed and evaluated. Labelling yield was higher than 95% for 125I as well asrnfor 177Lu. For 125I-DOTA-TATE the HPLC profile revealed two radiochemical species withrnretention times different from the unlabelled peptide, whilst for the other radiopeptides a singlernpeak was found. Stability was higher than 8 days for 125I-DOTA-TATE at 4℃ and -80℃, while forrn177Lu-DOTA-TATE was more than 24 hs at 4℃. Binding of radiopeptides to viable AR42J cellsrnincreased along time. Internalization experiments demonstrated that the radioconjugate penetratesrninto the cells reaching 73±14% (n=10), 32±9% (n=3) and 62±18% (n=6) of the peptide labelledrnwith 125I, 131I and 177Lu respectively in 3-4 hours. Biological uptake pattern of the radioidinatedrnpeptide indicates urinary as well as gastrointestinal excretion. In vivo metabolization is evidencedrnby thyroid uptake. In the case of labelling with 177Lu the elimination is mainly by urinary excretion.rnIn conclusion, DOTA-TATE labelled with radioiodine as well as with 177Lu were obtained with veryrnhigh yield, specific activity and ability to recognize and bind to somatostatin receptors present inrnviable tumor cells. Biodistribution in normal mice shows a different pattern when labelling withrnradioiodide and radiolantanide. These findings opens the possibility of the use of cocktails ofrnDOTA-TATE labelled with different radionuclides in order to minimize the radiation dose tornorgans not compromised with the tumor.