title: Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.
abstract: Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Garcia
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Fabio
authors.initials: F
authors.lastname: Gallazzi
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gambini
authors.forename: Williams
authors.initials: W
authors.lastname: Porcal
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, Montevideo 11400, Uruguay. pcabral@cin.edu.uy.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry*; D008024:Ligands; D008546:Melanoma, Experimental / Q000175:diagnosis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009539:Nicotinic Acids / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000737:chemistry*; D014018:Tissue Distribution; D000521:alpha-MSH / Q000737:chemistry*
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D002614:Chelating Agents; D006834:Hydrazines; D008024:Ligands; D009539:Nicotinic Acids; D015609:Organotechnetium Compounds; D010455:Peptides; D019275:Radiopharmaceuticals; C026058:EDDA; D000521:alpha-MSH; D004492:Edetic Acid; D005998:Glycine; C100184:tricine