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.