PET Imaging of the Neurotensin Targeting Peptide NOTA-NT-20.3 Using Cobalt-55, Copper-64 and Gallium-68

Abstract

Introduction: Neurotensin receptor 1 (NTSR1) is an emerging target for imaging and therapy of many types of cancer. Nuclear imaging of NTSR1 allows for noninvasive assessment of the receptor levels of NTSR1 on the primary tumor, as well as potential metastases. This work focuses on a the neurotensin peptide analogue NT-20.3 conjugated to the chelator NOTA for radiolabeling for use in noninvasive positron emission tomography (PET). NOTA-NT-20.3 was radiolabeled with gallium-68, copper-64, and cobalt-55 to determine the effect that modification of the radiometal has on imaging and potential therapeutic properties of NOTA-NT-20.3. Methods: In vitro assays investigating cell uptake and subcellular localization of the radiolabeled peptides were performed using human colorectal adenocarcinoma HT29 cells. In vivo PET/CT imaging was used to determine the distribution and clearance of the peptide in mice bearing NTSR1 expressing HT29 tumors. Results: Cell uptake studies showed that the highest uptake was obtained with [55Co] Co-NOTA-NT-20.3 (18.70 ± 1.30%ID/mg), followed by [64Cu] Cu-NOTA-NT-20.3 (15.46 ± 0.91%ID/mg), and lastly [68Ga] Ga-NOTA-NT-20.3 (10.94 ± 0.46%ID/mg) (p 55Co] Co-NOTA-NT-20.3 (20.28 ± 3.04) outperformed [64Cu] Cu-NOTA-NT-20.3 (6.52 ± 1.97). In conclusion, our studies show that enhanced cell uptake and increasing tumor to blood ratios over time displayed the superiority of [55Co] Co-NOTA-NT-20.3 over [68Ga] Ga-NOTA-NT-20.3 and [64Cu] Cu-NOTA-NT-20.3 for the targeting of NTSR1.

Keywords

• neurotensin
• PET
• cobalt-55
• copper-64
• gallium-68