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

[Image: see text] 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″-triaceti...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428032/
https://www.ncbi.nlm.nih.gov/pubmed/25615011
http://dx.doi.org/10.1021/acs.bioconjchem.5b00028
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author 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
author_facet 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
author_sort Kumar, Amit
collection PubMed
description [Image: see text] 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 T(1) 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.
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spelling pubmed-44280322015-05-13 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 Bioconjug Chem [Image: see text] 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 T(1) 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. American Chemical Society 2015-01-23 2015-03-18 /pmc/articles/PMC4428032/ /pubmed/25615011 http://dx.doi.org/10.1021/acs.bioconjchem.5b00028 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle 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
title Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes
title_full Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes
title_fullStr Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes
title_full_unstemmed Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes
title_short Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes
title_sort molecular platform for design and synthesis of targeted dual-modality imaging probes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428032/
https://www.ncbi.nlm.nih.gov/pubmed/25615011
http://dx.doi.org/10.1021/acs.bioconjchem.5b00028
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