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.
Original language | English (US) |
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Pages (from-to) | 277-288 |
Number of pages | 12 |
Journal | Theranostics |
Volume | 5 |
Issue number | 3 |
DOIs | |
State | Published - 2015 |
Keywords
- Copper 64
- Metal-chelating crosslinkers
- Metastases
- NOTA
- Nanogels
- PET
- Preclinical imaging
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)