Theranostics 2015; 5(3):277-288. doi:10.7150/thno.10904 This issue Cite
Research Paper
1. Skaggs School of Pharmacy and Pharmaceutical Sciences, and the Laboratory of Bioresponsive Materials, University of California, San Diego. 9500 Gilman Dr. 0600, La Jolla, CA 92093-0600, United States.
2. University of Pittsburgh Departments of Radiology, Pharmacology & Chemical Biology and Bioengineering. Molecular Imaging Laboratory, 100 Technology Drive, Pittsburgh, PA 15219, United States.
3. KACST-UCSD Center for Excellence in Nanomedicine and Engineering.
*These authors contributed equally.
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.
Keywords: Nanogels, metal-chelating crosslinkers, copper 64, PET, NOTA, preclinical imaging, metastases.