Perspective of pancreatic ductal adenocarcinoma imaging with 68Ga neurotensin analogues

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Authors: Marina Hodolič ^1,3; Feng Wang ²; Wenyu Wu ²; Pavel Koranda ³
Authors‘ workplace: Nuclear Medicine Research Department IASON, Graz, Austria, 2 Department of Nuclear Medicine, Nanjing First, Hospital, Nanjing, Medical University, Nanjing, China, 3 Klinika nukleární medicíny, LF UP Olomouc, ČR ¹
Published in: NuklMed 2021;10:63-67
Category: Review Article

Overview

Cells of pancreatic ductal adenocarcinoma (PDAC) express neurotensin receptors. Preclinical trials have successfully shown that neurotensin analogues have the potential for PET imaging of PDAC. Based on the published data, NTR-1 is promising target for the development of radioactive analogues for both imaging and therapy in patients with primary and metastatic pancreatic ductal adenocarcinoma. However, the first in vivo studies using ⁶⁸Ga DOTA-NT-20.3 in patients did not image PDAC tumours in all cases with very high contrast to surrounding tissue. Peptid research in the field of neurotensin analogues continues in an effort to further enhance the affinity of PET peptide radiopharmaceuticals for neurotensin receptors.

Keywords:

PET/CT – ancreatic cancer – neurotensin – in vivo human study

Sources

Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin 2019;69:7-34
Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the Pancreas: ESMO Clinical Practice Guidelines. Ann Oncol 2015;26: 56-68
National Comprehensive Cancer Network Website. NCCN guidelines version 1.2012: pancreatic adenocarcinoma. Available via [online]. 2011. [cit. 2021-05-22]. Dostupné na: http://nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.
Sakamoto T, Newman J, Fujimura M, et al. Role of neurotensin in pancreatic secretion. Surgery 1984;96:146 –153
Thor K, Rosell S. Neurotensin increases colonic motility. Gastroenterology 1986;90:27–31
Alifano M, Souazé F, Dupouy S, et al. Neurotensin receptor 1 determines the outcome of non-small cell lung cancer. Clin Cancer Res 2010;16:4401-4410
Wang JG, Li NN, Li HN, et al. Pancreatic cancer bears overexpression of neurotensin and neurotensin receptor subtype-1 and SR 48692 counteracts neurotensin induced cell proliferation in human pancreatic ductal carcinoma cell line PANC-1. Neuropeptides 2011;45:151-156
Baxendale IR, Cheung S, Kitching MO, et al. The synthesis of neurotensin antagonist SR 48692 for prostate cancer research. Bioorg Med Chem 2013;21:4378-4387
Yu J, Ren X, Chen Y, et al. Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients. PloS One 2013;8:56069
Bugni JM, Rabadi LA, Jubbal K, et al. The neurotensin receptor-1 promotes tumor development in a sporadic but not an inflammation-associated mouse model of colon cancer. Int J Cancer 2012;130:1798-1805
Dupouy S, Doan VK, Wu Z, et al. Activation of EGFR, HER2 and HER3 by neurotensin/neurotensin receptor 1 renders breast tumours aggressive yet highly responsive to lapatinib and metformin in mice. Oncotarget 2014;5:8235-8251
Qing Ouyang, Xueyang Gong, Hualiang Xiao, et al. Neurotensin promotes the progression of malignant glioma through NTSR1 and impacts the prognosis of glioma patients. Mol Cancer 2015;14:21
Guha S, Rey O, Rozengurt E. Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1. Cancer Res 2002;62:1632-1640
Wu Z, Martinez-Fong D, Trédaniel J, et al. Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy. Front Endocrinol (Lausanne) 2013; doi: 10.3389/fendo.2012.00184
Ehlers RA, Kim Sh, Zhang Y, et al. Gut peptide receptor expression in human pancreatic cancers. Ann Surg 2000;231:838–848
Reubi JC, Waser B, Friess H, et al. Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma. Gut 1998;42:546–550
Ouyang Q, Zhou J, Yang W, et al. Oncogenic role of neurotensin and neurotensin receptors in various cancers. Clin Exp Pharmacol Physiol 2017;44:841-846
Wang L, Friess H, Zhu Z, et al. Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease. Clin Cancer Res 2000;6:566-571
Yin X, Wang M, Wang H, et al. Evaluation of neurotensin receptor 1 as a potential imaging target in pancreatic ductal adenocarcinoma. Amino Acids 2017;49:1325-1335
He T, Wang M, Wang H, et al. Evaluation of neurotensin receptor 1 as potential biomarker for prostate cancer theranostic use. Eur J Nucl Med Mol Imaging 2019;46:2199-2207
Maschauer S, Einsiedel J, Hocke C, et al. Synthesis of a 68Ga-Labeled Peptoid−Peptide Hybrid for Imaging of Neurotensin Receptor Expression in Vivo. ACS Med Chem Lett 2010;1:15224-15228
Maschauer S, Einsiedel J, Haubner R, et al. Labeling and glycosylation of peptides using click chemistry: a general approach to 18F-glycopeptides as effective imaging probes for positron emission tomography. Angew Chem Int Ed 2010;49:976-979
Maschauer S, Einsiedel J, Hübner H, et al. 18F- and 68Ga-Labeled Neurotensin Peptides for PET Imaging of Neurotensin Receptor 1. J Med Chem 2016;59:6480-6492
Marenco M, Lodola L, Persico MG, et al. Evidence of 68Ga-DOTA-NT-20.3 Uptake in Pancreatic Adenocarcinoma AsPC-1 Cell Line - in vitro study. Curr Pharm Biotechnol 2018;19:754-759
Prignon A, Provost C, Alshoukr F, et al. Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis. Mol Pharm 2019;16:2776-2784
Hodolic M, Wu WY, Zhao Z, et al. Safety and tolerability of 68Ga-NT-20.3, a radiopharmaceutical for targeting neurotensin receptors, in patients with pancreatic ductal adenocarcinoma: the first in-human use. Eur J Nucl Med Mol Imaging. 2020;10.1007/s00259-020-05045-w. Epub ahead of print. PMID: 33006657.