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.