title: (68)Ga/DOTA- and (64)Cu/NOTA-phthalocyanine conjugates as fluorescent/PET bimodal imaging probes.
abstract: In this paper, we describe the synthesis and characterization of a series of new bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane-N,N'N″,N'″-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for PET imaging. The two moieties were linked through aliphatic chains of different lengths to modulate amphiphilicity. Labeling of DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7 h) was performed at 100 °C for 15 min with >90% efficiency for all conjugates. In vitro plasma stability assays demonstrated high stability of the (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to 7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results, we performed biodistribution studies on two (64)Cu-labeled derivatives, which allowed us to select a single candidate for preliminary in vivo experiments. Fluorescence and PET imaging confirmed the potential of these novel conjugates to act as bimodal probes.
authors: Centre d'imagerie moléculaire de Sherbrooke (CIMS), †Departments of Nuclear Medicine and Radiobiology and §Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke ; 3001 12th Avenue North, Sherbrooke, Québec, Canada J1H 5N4.
authors: Elena
authors: E
authors: Ranyuk
authors: Réjean
authors: R
authors: Lebel
authors: Yves
authors: Y
authors: Bérubé-Lauzière
authors: Klaus
authors: K
authors: Klarskov
authors: Roger
authors: R
authors: Lecomte
authors: Johan E
authors: JE
authors: van Lier
authors: Brigitte
authors: B
authors: Guérin
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007211:Indoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D054833:Isoindoles; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis; D061848:Optical Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D003301:Copper Radioisotopes; D005456:Fluorescent Dyes; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D007211:Indoles; D054833:Isoindoles; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; C013647:phthalocyanine