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

Research output: Contribution to journalArticle

10 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
Externally publishedYes

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Single-Photon Emission-Computed Tomography
Magnetic resonance imaging
Imaging techniques
Acids
Gadolinium
Tissue Distribution
Single photon emission computed tomography
Heterografts
Positron-Emission Tomography
Positron emission tomography
Pharmacokinetics
Magnetic resonance
Magnetic Resonance Imaging
Scaffolds
Ions
Peptides
Tumors
Injections
Tissue
Atoms

All Science Journal Classification (ASJC) codes

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

Cite this

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes. / Kumar, Amit; Zhang, Shanrong; Hao, Guiyang; Hassan, Gedaa; Ramezani, Saleh; Sagiyama, Koji; Lo, Su Tang; Takahashi, Masaya; Sherry, A. Dean; Öz, Orhan K.; Kovacs, Zoltan; Sun, Xiankai.

In: Bioconjugate Chemistry, Vol. 26, No. 3, 18.03.2015, p. 549-558.

Research output: Contribution to journalArticle

Kumar, A, Zhang, S, Hao, G, Hassan, G, Ramezani, S, Sagiyama, K, Lo, ST, Takahashi, M, Sherry, AD, Öz, OK, Kovacs, Z & Sun, X 2015, 'Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes', Bioconjugate Chemistry, vol. 26, no. 3, pp. 549-558. https://doi.org/10.1021/acs.bioconjchem.5b00028
Kumar, Amit ; Zhang, Shanrong ; Hao, Guiyang ; Hassan, Gedaa ; Ramezani, Saleh ; Sagiyama, Koji ; Lo, Su Tang ; Takahashi, Masaya ; Sherry, A. Dean ; Öz, Orhan K. ; Kovacs, Zoltan ; Sun, Xiankai. / Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes. In: Bioconjugate Chemistry. 2015 ; Vol. 26, No. 3. pp. 549-558.
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