摘要 |
The neuropeptideY(NPY)-receptor-subtype Y<SUB>1</SUB> is expressed differentially from breast tumor cells and is therefore an advantageous target molecule for the molecular imaging of breast cancer. Peptide analogs were synthesized, whose sequence is reduced to the receptor-binding sections of the natural ligand NPY. These Y<SUB>1</SUB> receptor-selective peptide analogs contain unnatural amino acids that increase the receptor affinity and are to ensure the stability of the greatly shortened peptide. New NPY analogs, which are to be used as radioligands, were tested for their binding affinity and selectivity for the Y<SUB>1</SUB> receptor. To this end, in-vitro binding tests with Y<SUB>1</SUB>- or Y<SUB>2</SUB> receptor-expressing cell lines were established and optimized. Then, the binding affinities of the NPY analogs were determined. In this case, a peptide (P2489) was identified, whose highest binding affinity was determined with a K<SUB>i</SUB> of 42.8 nmol of Y<SUB>1</SUB> receptor-expressing SK-N-MC cells and whose selectivity for the Y<SUB>1</SUB> receptor could be detected by the fact that there is no binding toY<SUB>2</SUB> receptor-expressing MHH-NB-11 cells. As an additional NPY analog, peptide fW7 contained the unnatural amino acid ?-aminocyclopropanecarboxylic acid on positions 32 and 34, by which the binding to the Y<SUB>1</SUB> receptor was influenced in a positive manner. A direct coupling of the chelating agent DOTA, which is necessary for the radiometal labeling of the peptides, to the N-terminal end of the peptides resulted in the loss of the binding affinity. By indirect coupling of the DOTA to the peptide fW7 via a spacer, this loss could be reduced, and fW7(DOTA) had a high binding affinity (K<SUB>i</SUB> = 62.8 nmol) similar to P2489. |