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Title: Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases

Abstract

Metals are essential in medicine for both therapy and diagnosis. We recently created the first metal-chelating nanogel imaging agent, which employed versatile, reproducible chemistry that maximizes chelation stability. Here we demonstrate that our metal chelating crosslinked nanogel technology is a powerful platform by incorporating 64Cu to obtain PET radiotracers. Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA). NOTA-based nanogels stably retained 64Cu in mouse serum and accumulated in tumors in vivo as detected by PET/CT imaging. Measurement of radioactivity in major organs ex vivo confirmed this pattern, revealing a high accumulation (12.3% ID/g and 16.6% ID/g) in tumors at 24 and 48 h following administration, with lower accumulation in the liver (8.5% ID/g at 24 h) and spleen (5.5% ID/g). Nanogels accumulated even more efficiently in metastases (29.9% and 30.4% ID/g at 24 and 48 h). These metal-chelating nanogels hold great promise for future application as bimodal PET/MRI agents; chelation of β-emitting radionuclides could enable radiation therapy.

Authors:
 [1];  [2];  [1];  [2];  [3]
+ Show Author Affiliations
  1. Univ. of California, San Diego, CA (United States). Skaggs School of Pharmacy and Pharmaceutical Sciences. Lab. of Bioresponsive Materials
  2. Univ. of Pittsburgh, PA (United States). Depts. of Radiology, Pharmacology & Chemical Biology and Bioengineering. Molecular Imaging Lab.
  3. Univ. of California, San Diego, CA (United States). Skaggs School of Pharmacy and Pharmaceutical Sciences. Lab. of Bioresponsive Materials. KACST-UCSD Center for Excellence in Nanomedicine and Engineering
Publication Date:
Research Org.:
Univ. of Pittsburgh, PA (United States); Univ. of California, San Diego, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States); National Science Foundation (NSF)
OSTI Identifier:
1455056
Grant/Contract Number:  
SC0008833; DP 2OD006499; P30CA047904; 1006081
Resource Type:
Accepted Manuscript
Journal Name:
Theranostics
Additional Journal Information:
Journal Volume: 5; Journal Issue: 3; Journal ID: ISSN 1838-7640
Publisher:
Ivyspring
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; nanogels; metal-chelating crosslinkers; copper 64; PET; NOTA; preclinical imaging; metastases

Citation Formats

Lux, Jacques, White, Alexander G., Chan, Minnie, Anderson, Carolyn J., and Almutairi, Adah. Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases. United States: N. p., 2015. Web. doi:10.7150/thno.10904.
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Lux, Jacques, White, Alexander G., Chan, Minnie, Anderson, Carolyn J., & Almutairi, Adah. Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases. United States. https://doi.org/10.7150/thno.10904
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Lux, Jacques, White, Alexander G., Chan, Minnie, Anderson, Carolyn J., and Almutairi, Adah. Thu . "Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases". United States. https://doi.org/10.7150/thno.10904. https://www.osti.gov/servlets/purl/1455056.
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@article{osti_1455056,
title = {Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases},
author = {Lux, Jacques and White, Alexander G. and Chan, Minnie and Anderson, Carolyn J. and Almutairi, Adah},
abstractNote = {Metals are essential in medicine for both therapy and diagnosis. We recently created the first metal-chelating nanogel imaging agent, which employed versatile, reproducible chemistry that maximizes chelation stability. Here we demonstrate that our metal chelating crosslinked nanogel technology is a powerful platform by incorporating 64Cu to obtain PET radiotracers. Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA). NOTA-based nanogels stably retained 64Cu in mouse serum and accumulated in tumors in vivo as detected by PET/CT imaging. Measurement of radioactivity in major organs ex vivo confirmed this pattern, revealing a high accumulation (12.3% ID/g and 16.6% ID/g) in tumors at 24 and 48 h following administration, with lower accumulation in the liver (8.5% ID/g at 24 h) and spleen (5.5% ID/g). Nanogels accumulated even more efficiently in metastases (29.9% and 30.4% ID/g at 24 and 48 h). These metal-chelating nanogels hold great promise for future application as bimodal PET/MRI agents; chelation of β-emitting radionuclides could enable radiation therapy.},
doi = {10.7150/thno.10904},
journal = {Theranostics},
number = 3,
volume = 5,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2015},
month = {Thu Jan 01 00:00:00 EST 2015}
}
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https://doi.org/10.7150/thno.10904
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