Molecular platform for design and synthesis of targeted dual-modality imaging probes

Bioconjug Chem. 2015 Mar 18;26(3):549-58. doi: 10.1021/acs.bioconjchem.5b00028. Epub 2015 Feb 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Design*
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / metabolism
  • Gadolinium / analysis
  • Gadolinium / chemistry*
  • Gadolinium / metabolism
  • Gallium Radioisotopes / analysis
  • Gallium Radioisotopes / chemistry*
  • Gallium Radioisotopes / metabolism
  • Humans
  • Isotopes
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Positron-Emission Tomography / methods
  • Rats
  • Tissue Distribution / physiology
  • Xenograft Model Antitumor Assays / methods


  • Fluorescent Dyes
  • Gallium Radioisotopes
  • Isotopes
  • Gadolinium