PEG‐poly(L‐lysine)‐based polymeric micelle MRI contrast agent: Feasibility study of a Gd‐micelle contrast agent for MR lymphography

• Published in: Journal of magnetic resonance imaging Vol. 47; no. 1; pp. 238 - 245
• Main Authors: Akai, Hiroyuki, Shiraishi, Kouichi, Yokoyama, Masayuki, Yasaka, Koichiro, Nojima, Masanori, Inoue, Yusuke, Abe, Osamu, Ohtomo, Kuni, Kiryu, Shigeru
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018
• Subjects: Animals; Aorta; Area Under Curve; Biopsy; contrast agent; Contrast agents; Contrast Media - chemistry; Coordination Complexes - chemistry; Factorial analysis; Feasibility Studies; Female; Fluorocarbons - chemistry; Freund's Adjuvant; Gadolinium; Gadolinium - chemistry; Image Processing, Computer-Assisted; Inflammation; Lymph nodes; Lymph Nodes - diagnostic imaging; Lymphatic system; Lymphography; Lysine; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Micelles; MR lymphography; Polyethylene glycol; Polyethylene Glycols - chemistry; Polylysine - chemistry; Qualitative analysis; Sacrum; Variance analysis; inflammation; MR lymphography; contrast agent
• DOI: 10.1002/jmri.25740
• ISSN: 1053-1807

Purpose To investigate the feasibility of polymeric micelle of poly(ethyleneglycol) (PEG)‐b‐poly(L‐lysine‐DOTA) (Gd‐micelle) as a contrast agent for magnetic resonance lymphography (MRL). Materials and Methods Twenty‐four female BALB/c mice were randomly divided into four groups of six mice each. Among them, mice of two groups were injected of complete Freund's adjuvant to obtain inflamed lymph nodes. We subcutaneously injected 0.5 μmol Gd per mouse of Gd‐micelle or gadofluorine P in the right rear footpad. Identical 3D T1‐weighted gradient‐echo imaging (1T MRI system) were subsequently obtained to create time–intensity curves of the right popliteal, sacral, and lumbar‐aortic lymph nodes and to measure the contrast ratios (CRs). The peak CR, area under the curve (AUC), and elimination half‐life (T1/2) of CR of the popliteal lymph node were assessed by two‐way factorial analysis of variance. We also performed a qualitative assessment of normal and inflamed lymph node at three timepoints. Results The mean peak CR of Gd‐micelle was 2.64 and 1.89 for gadofluorine P in normal mice, and 3.48 and 2.73 in the inflamed lymph node. Statistically, peak CR was higher for Gd‐micelle (P = 0.004). In addition, the AUC was larger (P < 0.001) and T1/2 was longer (P < 0.001) for Gd‐micelle. In qualitative assessment, Gd‐micelle demonstrated the same or higher scores in every lymph node, and demonstrated a higher score in lumbar‐aortic lymph node of a 360‐minute image (P = 0.006) and in inflamed lymph node of a 360‐minute image (P = 0.009). Conclusion Compared to gadofluorine P, Gd‐micelle showed higher and more prolonged enhancement in MRL imaging in normal and inflamed lymph nodes. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:238–245.