(18)F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y(1)R for PET imaging of mammary carcinoma

Neuropeptide Y Y(1) receptors (Y(1)R) 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 Y(1)R 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 Y(1)R 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 Y(1)R. Three new radioligands based on BIBP3226, bearing an (18)F-fluoroethoxy linker (12), an (18)F-PEG-linker (13) or an (18)F-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayed Y(1)R 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 Y(1)R affinities. Although 12 and 13 showed displaceable and specific binding to Y(1)R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios for Y(1)R imaging by PET. Yet the present study is another step towards an optimized PET radioligand for imaging of Y(1)R in vivo.