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.

Recent advances in the preparation and application of multifunctional iron oxide and liposome-based nanosystems for multimodal diagnosis and therapy

“…For example, radiolabelled poly(aspartic acid)-coated and PLGA-coated IONPs were used in two different studies for PET/MRI scanner of tumour integrin a v b 3 expression [72,73]. IONPs were coupled to RGD peptide and DOTA chelator prior to labelling with 64 Cu.…”

Multistage vector (MSV) therapeutics

“…Nevertheless, the application of the MSV delivery system in not restricted to the use of these nanoparticles. In actuality, the platform has also been used for the delivery of contrast agents [20, 113, 114], quantum dots [115, 116], and carbon nanotubes [116] for diagnostic and imaging purposes, indicating that the MSV would be well-suited as a theranostic platform. A major advantage of employing MSVs for imaging purposes is that the relaxivity of contrast agents can be improved as a result of geometrical confinement.…”

Opportunities for nanotheranosis in lung cancer and pulmonary metastasis

“…Both conventional spherical NPs and discoidal nanoconstructs can be loaded with a variety of drug molecules, including potent chemotherapeutic molecules, such as doxorubicin, docetaxel, paclitaxel [21–23], and labeled with multiple contrast agents, including infra-red and near infrared dyes (for optical imaging) [22]; Gd 3+ -ions and iron oxide nanocrystals (for magnetic resonance imaging: MRI) [23–27]; radioisotopes (for nuclear imaging) [28]; and iodine molecules and gold nanoparticles (for CT imaging).…”

“…Our group has been synthesizing spherical, polymeric-phospholipid NPs by means of a nano-precipitation method [28]. These NPs present a hydrodynamic diameter of about 150 nm, a ξ-potential of −35.0 mV, and are sufficiently small to rely on the EPR effect for tumor accumulation [29–31].…”

“…PET imaging and MRI of spherical nanoparticles accumulating within the breast tumor tissue at ~ 20h p.i.. Nanoparticles mostly accumulate at the periphery of the malignant mass, as dictated by the EPR effect. Rearranged from Aryal et al 2014 [28]. …”