Accuracy of equilibrium magnetization mapping in sliced two-dimensional spoiled gradient-recalled echo pulse sequence with variable flip angle.

PURPOSE: To evaluate the accuracy of an equilibrium magnetization (M0 ) map obtained using a two-dimensional (2D) spoiled gradient-recalled echo (SPGR) pulse sequence with variable flip angle (VFA). MATERIALS AND METHODS: Single-slice 2D SPGR images of 4% agar gel phantoms with different gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) concentrations (0-1 mM) were obtained with a VFA (2-30°). The 2D SPGR-VFA data were acquired with different repetition times (TRs; 7.8-117.2 ms), Gaussian and sinc RF pulses, and different field strengths (4.7, 7, and 9.4 Tesla). M0 and T1 maps were calculated from the 2D SPGR-VFA data. M0 and T1 values were compared with those calculated from free-relaxed 2D gradient-recalled echo (GRE) images and inversion recovery-prepared 2D SPGR images. The M0 and T1 slice profiles were also investigated. RESULTS: Consistent M0 values were obtained, regardless of the different Gd concentrations, TRs, and pulse sequences. The M0 slice profiles calculated from the sliced SPGR-VFA data quantitatively reproduced those calculated from the free-relaxed sliced GRE. In contrast, the T1 values calculated from the 2D SPGR-VFA data were underestimated at a high Gd concentration, short TR, and Gaussian RF pulse. CONCLUSION: M0 values calculated from 2D SPGR-VFA images are highly quantitative.

Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-ß type I receptor inhibitor.

Tumor cell targeting of drug carriers is a promising strategy and uses the attachment of various ligands to enhance the therapeutic potential of chemotherapy agents. Folic acid is a high-affinity ligand for folate receptor, which is a functional tumor-specific receptor. The transforming growth factor (TGF)-ß type I receptor (TßR-I) inhibitor A-83-01 was expected to enhance the accumulation of nanocarriers in tumors by changing the microvascular environment. To enhance the therapeutic effect of folate-linked liposomal doxorubicin (F-SL), we co-administrated F-SL with A-83-01. Intraperitoneally injected A-83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A-83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A-83-01 temporarily changed the tumor vasculature around 3 h post injection. A-83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A-83-01 showed significantly greater antitumor activity than F-SL alone. This study shows that co-administration of TßR-I inhibitor will open a new strategy for the use of FR-targeting nanocarriers for cancer treatment.

Accelerated blood clearance was not induced for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle in mice.

PURPOSE: Accelerated blood clearance (ABC) is induced by repeated injections of PEGylated liposomes. In this study, the ABC was investigated for a gadolinium-containing PEG-poly(L-lysine)-based polymeric micelle (Gd-micelle) and PEGylated liposome (Gd-liposome) in mice. MATERIALS AND METHODS: Effects of the first injection of Gd-micelle on the tissue distribution of the second dose of Gd-micelle were studied. Additionally, effects of the first injection of Gd-micelle, Gd-liposome, empty liposome, polyethyleneglycol (PEG(500,000)), and PEG-lipid on the distribution of the second dose of the Gd-liposome were evaluated. RESULTS: Results indicated that the tissue distribution of the second injection of the Gd-micelle at a dose of 33, 5, or 2 micromol Gd/kg was not affected by the first injection of the Gd-micelle at different doses and time intervals or of the empty PEGylated liposome 7 days before. ABC of Gd-liposome at a dose of 2.3 micromol Gd/kg (corresponding to 10 micromol lipids/kg) was observed when the empty PEGylated liposome or Gd-liposome, but not the Gd-micelle, PEG(500,000) or PEG-lipid, was pre-administered. CONCLUSIONS: The hydrophobic core of the micelle or lipid bilayer of PEGylated liposome has a major effect on this phenomenon. These studies have significant implications for the evaluation of PEG-poly(L-lysine)-based micellar formulation of Gd-based contrast agents.

Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents.

A polymeric micelle drug carrier system was applied to the targeting of an MRI (magnetic resonance imaging) contrast agent. A block copolymer, PEG-b-poly(L-lysine), was used for conjugation of gadolinium ions through chelating moieties, DOTA. The DOTA moieties were successfully conjugated to all primary amine groups of the lysine residues. The obtained block copolymer, PEG-b-poly(L-lysine-DOTA), formed a polymeric micelle. The polymeric micelle structure was maintained even after partial gadolinium chelation ( approximately 40%) to the DOTA moieties. The prepared polymeric micelle MRI contrast agent was injected into a mouse tail vein at a dose of 0.05 mmol Gd/kg. The polymeric micelle-based MRI contrast agent exhibited stable blood circulation. A considerable amount (6.1+/-0.3% of ID/g of the polymeric micelle) was found to accumulate at solid tumors 24 h after intravenous injection by means of the EPR effect. An MRI analysis revealed that the signal intensity of the tumor was enhanced 2.0-fold by the use of this contrast agent.