Liposomes for PET and MR Imaging and for Dual Targeting (Magnetic Field/Glucose Moiety): Synthesis, Properties, and in Vivo Studies

Abstract

We describe the potentiality of a new liposomal formulation enabling positron emission tomography (PET) and magnetic resonance MR() imaging. The bimodality is achieved by coupling a Ga-based radiotracer on the bilayer of magnetic liposomes. In order to enhance the targeting properties obtained under a permanent magnetic field, a sugar moiety was added in the lipid formulation. Two new phospholipids were synthesized, one with a specific chelator ofGa (DSPE-PEG-NODAGA) and one with a glucose moiety (DSPE-PEG-glucose). The liposomes were produced according to a fast and safe process, with a high radiolabeling yield. MR and PET imaging were performed on mice bearing human glioblastoma tumors (U87MG) after iv injection. The accumulation of the liposomes in solid tumor is evidenced by MR imaging and the amount is evaluated in vivo and ex vivo according to PET imaging. An efficient magnetic targeting is achieved with these new magnetic liposomes.

In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic Liposomes Monitored by MRI

“…Magnetic nanoparticles and magnetic systems have already been conjugated with PET radiotracers [25]. However, the strategies rely on the incorporation of a specific chelator inside or on the surface of nanoparticles involving constraints related to the manipulation of radioactive species.…”

Multimodality Imaging Agents with PET as the Fundamental Pillar

“…[14] 2.1.1. [14] Since the pioneering work on PET/MR dual-modality imaging of tumor integrin expression using 64 Cu-labeled and arginine-glycine-aspartic (RGD)-conjugated IONPs, [15] much work has been focused on radiolabeling IONPs with various isotopes,i ncluding short-lived isotopes such as 11 C(t 1/2 = 20.4 min), [16]6 8 Ga (t 1/2 = 67.7 min), [17] and 18 F (t 1/2 = 109.8 min), [18] and longer-lived isotopes such as 64 Cu (t 1/2 = 12.7 h), [19] 72 As (t 1/2 = 26 h), [20]6 9 Ge (t 1/2 = 39.05 h), [21] 89 Zr (t 1/2 = 78.4 h), [22] and 124 I( t 1/2 = 4.2 d). [14] Since the pioneering work on PET/MR dual-modality imaging of tumor integrin expression using 64 Cu-labeled and arginine-glycine-aspartic (RGD)-conjugated IONPs, [15] much work has been focused on radiolabeling IONPs with various isotopes,i ncluding short-lived isotopes such as 11 C(t 1/2 = 20.4 min), [16]6 8 Ga (t 1/2 = 67.7 min), [17] and 18 F (t 1/2 = 109.8 min), [18] and longer-lived isotopes such as 64 Cu (t 1/2 = 12.7 h), [19] 72 As (t 1/2 = 26 h), [20]6 9 Ge (t 1/2 = 39.05 h), [21] 89 Zr (t 1/2 = 78.4 h), [22] and 124 I( t 1/2 = 4.2 d).…”

“…PET/T 2 -MR Imaging IONPs act as CAst os horten the transverse (T 2 ) relaxation time of nearby water molecules,r esulting in negative contrast enhancement (darker image) in T 2 -weighted MR imaging. [14] Since the pioneering work on PET/MR dual-modality imaging of tumor integrin expression using 64 Cu-labeled and arginine-glycine-aspartic (RGD)-conjugated IONPs, [15] much work has been focused on radiolabeling IONPs with various isotopes,i ncluding short-lived isotopes such as 11 C(t 1/2 = 20.4 min), [16]6 8 Ga (t 1/2 = 67.7 min), [17] and 18 F (t 1/2 = 109.8 min), [18] and longer-lived isotopes such as 64 Cu (t 1/2 = 12.7 h), [19] 72 As (t 1/2 = 26 h), [20]6 9 Ge (t 1/2 = 39.05 h), [21] 89 Zr (t 1/2 = 78.4 h), [22] and 124 I( t 1/2 = 4.2 d). [23] Tr aditional radiolabeling strategies involve conjugating the polymeric surface coatings of IONPs with chelators such as DFO (desferrioxamine B) for 89 Zr coordination, [22] tyrosine residues for 124 Ib inding, [23] and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for 64 Cu chelation.…”

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

“…For this purpose, liposomes are either labeled or loaded with both, the therapeutic agent and the imaging probe. Visualization of liposomes with T 1 -weighted MRI [115,116] and T 2 -weighted MRI [117], PET [118][119][120] and OI [121], among others, has been achieved in several studies.…”

“…Fused PET/MR images acquired 20 min revealed major liver and spleen accumulation. Malinge et al [119] synthesized DSPE-PEGylated liposomes loaded with maghemite nanoparticles in their lumen in order to perform magnetic targeting and use them as MRI contrast agents. They incorporated glucose in the lipid formulation as an extra tumor-targeting moiety.…”