title: Molecular platform for design and synthesis of targeted dual-modality imaging probes.
abstract: We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N',N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of (68/67)Ga(3+) and Gd(3+), respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM(-1) s(-1) at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with (67)Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection.
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Shanrong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Hao
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Gedaa
authors.initials: G
authors.lastname: Hassan
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Saleh
authors.initials: S
authors.lastname: Ramezani
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Koji
authors.initials: K
authors.lastname: Sagiyama
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Su-Tang
authors.initials: ST
authors.lastname: Lo
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Orhan K
authors.initials: OK
authors.lastname: Öz
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.affiliation: †Department of Radiology, ‡Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D005456:Fluorescent Dyes / Q000032:analysis / Q000138:chemical synthesis* / Q000378:metabolism; D005682:Gadolinium / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D005710:Gallium Radioisotopes / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007554:Isotopes; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D014018:Tissue Distribution / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D005456:Fluorescent Dyes; D005710:Gallium Radioisotopes; D007554:Isotopes; D005682:Gadolinium