title: Positron emitting magnetic nanoconstructs for PET/MR imaging.
abstract: Hybrid PET/MRI scanners have the potential to provide fundamental molecular, cellular, and anatomic information essential for optimizing therapeutic and surgical interventions. However, their full utilization is currently limited by the lack of truly multi-modal contrast agents capable of exploiting the strengths of each modality. Here, we report on the development of long-circulating positron-emitting magnetic nanoconstructs (PEM) designed to image solid tumors for combined PET/MRI. PEMs are synthesized by a modified nano-precipitation method mixing poly(lactic-co-glycolic acid) (PLGA), lipids, and polyethylene glycol (PEG) chains with 5 nm iron oxide nanoparticles (USPIOs). PEM lipids are coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and subsequently chelated to (64)Cu. PEMs show a diameter of 140 ± 7 nm and a transversal relaxivity r2 of 265.0 ± 10.0 (mM × s)(-1), with a r2/r1 ratio of 123. Using a murine xenograft model bearing human breast cancer cell line (MDA-MB-231), intravenously administered PEMs progressively accumulate in tumors reaching a maximum of 3.5 ± 0.25% ID/g tumor at 20 h post-injection. Correlation of PET and MRI signals revealed non-uniform intratumoral distribution of PEMs with focal areas of accumulation at the tumor periphery. These long-circulating PEMs with high transversal relaxivity and tumor accumulation may allow for detailed interrogation over multiple scales in a clinically relevant setting.
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX, 77030, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Aryal
authors.forename: Jaehong
authors.initials: J
authors.lastname: Key
authors.forename: Cinzia
authors.initials: C
authors.lastname: Stigliano
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Landis
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Lee
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
mesh_terms: D000818:Animals; D004583:Electrons; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography
keywords: PET-MRI; hybrid imaging; iron oxide nanoparticles; molecular imaging; polymer-lipid nanoparticles