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.