Synthesis of oxytocin HYNIC derivatives as potential diagnostic agents for breast cancer.
Two synthetic procedures for HYNIC oxytocin labeling were developed: one based on an orthogonal protection approach and the other with prelabeled (Boc)HYNIC-(Fmoc) amino acids. Both procedures were compared and applied to the preparation of several HYNIC-oxytocin derivatives where ligand position and amino acid (lysine and phenylalanine) were varied. Additionally, an oxytocin derivative labeled with HYNIC in the alpha-amino group of the Cys1 residue was also prepared. 99mTc-ethylendiaminediacetic acid (EDDA) labeling efficiencies were examined for all the derivatives, resulting in two candidates which showed affinity for the oxytocin receptor. Further biochemical experiments demonstrated that 99mTc-EDDA/HYNIC-Cys1-OT-CONH2 could be used as a potential radiopharmaceutical for breast cancer diagnosis.
Instituto de Investigaciones Científicas, Universidad de Guanajuato, Guanajuato, Gto. Mexico.
Alma D
AD
Miranda-Olvera
Guillermina
G
Ferro-Flores
Martha
M
Pedraza-López
Consuelo Arteaga
CA
de Murphy
Luis M
LM
De León-Rodríguez
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis*; D008239:Lysine / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D009539:Nicotinic Acids / Q000138:chemical synthesis*; D015609:Organotechnetium Compounds / Q000737:chemistry; D010121:Oxytocin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000737:chemistry; D011877:Radionuclide Imaging / Q000379:methods*; D019275:Radiopharmaceuticals; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry; D013194:Staining and Labeling; D017556:Technetium Compounds / Q000737:chemistry; D013997:Time Factors
C120392:6-hydrazinopyridine-3-carboxylic acid; D000596:Amino Acids; C482294:CYS1 protein, human; C449819:Cys1 protein, mouse; D005449:Fluorenes; D006834:Hydrazines; D008565:Membrane Proteins; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009539:Nicotinic Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D010649:Phenylalanine; D010121:Oxytocin; D013004:Somatostatin; C026058:EDDA; D004492:Edetic Acid; C444119:technetium Tc 99m depreotide; D008239:Lysine