18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET imaging of mammary carcinoma
Maschauer S, Ott J, Bernhardt G, Kuwert T, Keller M, Prante O (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 9
Pages Range: 12990-
Journal Issue: 1
DOI: 10.1038/s41598-019-49399-0
Abstract
Neuropeptide Y Y1 receptors (Y1R) have been found to be overexpressed in a number of different tumours, such as breast, ovarian or renal cell cancer. In mammary carcinoma the high Y1R density together with its high incidence of 85% in primary human breast cancers and 100% in breast cancer derived lymph node metastases attracted special attention. Therefore, the aim of this study was the development of radioligands for Y1R imaging by positron emission tomography (PET) with a special emphasis on imaging agents with reduced lipophilicity to provide a PET ligand with improved biodistribution in comparison with previously published tracers targeting the Y1R. Three new radioligands based on BIBP3226, bearing an 18F-fluoroethoxy linker (12), an 18F-PEG-linker (13) or an 18F-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayed Y1R affinities of 2.8 nM (12), 29 nM (13) and 208 nM (11) and were characterised in vitro regarding binding to human breast cancer MCF-7-Y1 cells and slices of tumour xenografts. In vivo, small animal PET studies were conducted in nude mice bearing MCF-7-Y1 tumours. The binding to tumours, solid tumour slices and tumour cells correlated well with the Y1R affinities. Although 12 and 13 showed displaceable and specific binding to Y1R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios for Y1R imaging by PET. Yet the present study is another step towards an optimized PET radioligand for imaging of Y1R in vivo.
Authors with CRIS profile
Simone Maschauer
Department of Nuclear Medicine
Torsten Kuwert
Lehrstuhl für Klinische Nuklearmedizin
Olaf Prante
Professur für Molekulare Bildgebung und Radiochemie
Involved external institutions
Germany (DE)How to cite
APA:
Maschauer, S., Ott, J., Bernhardt, G., Kuwert, T., Keller, M., & Prante, O. (2019). 18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET imaging of mammary carcinoma. Scientific Reports, 9(1), 12990-. https://dx.doi.org/10.1038/s41598-019-49399-0
MLA:
Maschauer, Simone, et al. "18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET imaging of mammary carcinoma." Scientific Reports 9.1 (2019): 12990-.
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