title: [99mTc(CO)3]+ and [99mTcO2]+ radiolabeled cyclic melanotropin peptides for melanoma SPECT imaging.
abstract: The melanoma targeting peptides (Ala-triazol)Ac-Re(Arg(11))CCMSH and N4-CO-Re(Arg(11))CCMSH were radiolabeled with [(99m)Tc(CO)3](+) and [(99m)TcO2](+), respectively, and examined for in vitro cell binding, in vivo biodistribution and imaging properties. The (Ala-triazol)Ac-Re(Arg(11))CCMSH and N4-CO-Re(Arg(11))CCMSH were synthesized as protected peptides on resin followed by rhenium cyclization with [(C6H5)3P]2ReOCl3 in DMF. The peptides were labeled with (99m)Tc and examined for radiochemical stability and melanoma cell binding. In vivo biodistribution and SPECT/CT imaging studies were performed in B16/F1 melanoma tumor bearing C57 mice. (99m)Tc(CO)3-(Ala-Triazol)Ac- Re(Arg(11))CCMSH and (99m)TcO2-N4-CO-Re(Arg(11))CCMSH were stable and internalized in B16/F1 melanoma cells upon binding. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-(Ala-Triazol)Ac-Re(Arg(11))CCMSH was 6.08±1.06% ID/g and 7.05±1.48% ID/g at 2 h and 4 h post injection, respectively. Tumor uptake of (99m)TcO2-N4-CORe(Arg(11))CCMSH was 7.54±1.82% ID/g and 2.28±0.22% ID/g at 1 h and 2 h post injection, respectively. SPECT/CT imaging studies showed that tumor selective uptake of the radiolabeled peptides, which was confirmed by competitive blocking studies.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.forename: Vania
authors.initials: V
authors.lastname: Teixeira
authors.forename: Williams
authors.initials: W
authors.lastname: Porcal
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Gambini
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.forename: Fabio
authors.initials: F
authors.lastname: Gallazzi
authors.affiliation: Biochemistry Department, 117 Schweitzer Hall, University of Missouri, Columbia MO 65211 USA. QuinnT@missouri.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Quinn
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D005260:Female; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009074:Melanocyte-Stimulating Hormones; D008545:Melanoma / Q000000981:diagnostic imaging*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D013667:Technetium; D017556:Technetium Compounds; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D000588:Amines; D002614:Chelating Agents; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D017556:Technetium Compounds; C561418:dioxotechnetium; D013667:Technetium; D009074:Melanocyte-Stimulating Hormones