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 (64)Cu to obtain PET radiotracers. Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA). NOTA-based nanogels stably retained (64)Cu 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.affiliation: 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.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lux
authors.affiliation: 2. University of Pittsburgh Departments of Radiology, Pharmacology & Chemical Biology and Bioengineering. Molecular Imaging Laboratory, 100 Technology Drive, Pittsburgh, PA 15219, United States.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: White
authors.affiliation: 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.
authors.forename: Minnie
authors.initials: M
authors.lastname: Chan
authors.affiliation: 2. University of Pittsburgh Departments of Radiology, Pharmacology & Chemical Biology and Bioengineering. Molecular Imaging Laboratory, 100 Technology Drive, Pittsburgh, PA 15219, United States.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: 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. ; 3. KACST-UCSD Center for Excellence in Nanomedicine and Engineering.
authors.forename: Adah
authors.initials: A
authors.lastname: Almutairi
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D051379:Mice; D000080385:Nanogels; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009369:Neoplasms / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D003301:Copper Radioisotopes; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
keywords: NOTA; Nanogels; PET; copper 64; metal-chelating crosslinkers; metastases.; preclinical imaging