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Development and characterization of two novel 68 Ga‐labelled neuropeptide Y short analogues with potential application in breast cancer imaging
Author(s) -
Cardoso María Elena,
Tejería Emilia,
Zirbesegger Kevin,
Savio Eduardo,
Terán Mariella,
Rey Ríos Ana María
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13864
Subject(s) - biodistribution , chemistry , lipophilicity , lysine , internalization , in vivo , amino acid , breast cancer , linker , imaging agent , in vitro , biochemistry , receptor , cancer , medicine , biology , microbiology and biotechnology , computer science , operating system
In vivo receptor targeting with radiolabelled peptide‐based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε‐amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga‐L1 and (4.7 ± 0.4) for 68 Ga‐L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.