Abstract
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Objectives Neurotensin receptors (NTR) are expressed in a number of cancers such as human ductal pancreatic adenocarcinoma (75%), colon adenocarcinoma, and invasive ductal breast cancer (91%). This work aims to develop a PET imaging agent using a new neurotensin analogue NT(6-13), Ac-K(NOTA)-P-NMeArg-RPY-Tle-L (NTA1) thereby enabling early detection of the neurotensin receptor (NTR) positive cancers.
Methods The neurotensin analogue Ac-K(NOTA)-P-NMeArg-RPY-Tle-L was selected for this study and was obtained from CPC scientific. In vitro studies of[ 64Cu]Ac-K(NOTA)-P-NMeArg-RPY-Tle-L were conducted using human colon adenocarcinoma HT29 cell lines. In vivo studies were also carried out using nude mice bearing HT29 xenografts.
Results The neurotensin analogue Ac-K(NOTA)-P-NMeArg-RPY-Tle-L was labeled with 64Cu with 1.2 mCi/µg (1660 mCi/µmol or 61.4 GBq/µmol) specific activity and exhibited high binding ( Kd= 4.8 + 2.8 nM) in HT29 cells. Bound activity was internalized quickly. A blocking study with “cold” peptides confirmed the specificity of binding. PET imaging and post-PET biodistribution analysis demonstrated tumor uptake, tumor/muscle ratio was 12 and the tumor (unblocked) uptake was 5 times of the tumor (blocked).
Conclusions The high binding and specificity of [64Cu] Ac-K(NOTA)-P-NMeArg-RPY-Tle-L make it an excellent candidate as a PET imaging agent for the detection of a number of NTR expressing tumors. In vivo and invitro characterization of [68Ga]Ac-K(NOTA)-P-NMeArg-RPY-Tle-L is also underway