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Positron Emitting Magnetic Nanoconstructs for PET/MR Imaging
Author(s) -
Aryal Santosh,
Key Jaehong,
Stigliano Cinzia,
Landis Melissa D.,
Lee Daniel Y.,
Decuzzi Paolo
Publication year - 2014
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201303933
Subject(s) - dota , materials science , positron emission tomography , polyethylene glycol , biomedical engineering , magnetic resonance imaging , nuclear medicine , nanoparticle , chelation , cancer research , chemistry , medicine , nanotechnology , radiology , biochemistry , metallurgy
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 r 2 of 265.0 ± 10.0 (mM × s) −1 , with a r 2 /r 1 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.