Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

Amit Kumar, Shanrong Zhang, Guiyang Hao, Gedaa Hassan, Saleh Ramezani, Koji Sagiyama, Su Tang Lo, Masaya Takahashi, A. Dean Sherry, Orhan K. Öz, Zoltan Kovacs, Xiankai Sun

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12 Citations (Scopus)

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 68/67Ga3+ and Gd3+, 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 67Ga. 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.

Original languageEnglish
Pages (from-to)549-558
Number of pages10
JournalBioconjugate Chemistry
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 18 2015

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Kumar, A., Zhang, S., Hao, G., Hassan, G., Ramezani, S., Sagiyama, K., Lo, S. T., Takahashi, M., Sherry, A. D., Öz, O. K., Kovacs, Z., & Sun, X. (2015). Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes. Bioconjugate Chemistry, 26(3), 549-558. https://doi.org/10.1021/acs.bioconjchem.5b00028