Lymph Node Metastases Detection Using Gd₂O₃@PCD as Novel Multifunctional Contrast Imaging Agent in Metabolic Magnetic Resonance Molecular Imaging

Abstract

Axillary lymph node detection is crucial to staging and prognosis of the lymph node metastatic spread in breast cancer. Currently, lymphoscintigraphy and blue dye, as the conventional methods to localize sentinel lymph nodes (SLNs), are invasive and can only be performed during surgery. This study has had a novel hybrid gadolinium oxide nanoparticle coating with Cyclodextrin-based polyester as a high-relaxivity T1 magnetic resonance molecular imaging (MRMI) contrast agent (CA). Twelve female BALB/c mice were randomly divided into three groups of four mice; each group was injected with 4T1 cells to obtain metastasis lymph nodes and diagnosed by using the 3D T1W (VIBE) MRI (Siemens 3T, Prisma). The synthesized Gd2O3@PCD nanoparticles with a suitable particle size range of 20–40 nm have had much higher longitudinal relaxivity (r1) for Gd2O3@PCD and Gd-DOTA (Dotarem) with the values of 3.98 mM−1·s−1 ± 0.003 and 2.71 mM−1·s−1 ± 0.005, respectively. Identical MR images in coronal views were subsequently obtained to create time-intensity curves of the right axillary lymph nodes and to measure the contrast ratio (CR). The peak CR and qualitative assessment of axillary lymph nodes at five-time points were evaluated. After subcutaneous injection, the contrast ratio of axillary lymph node and tumor in mice exhibited CR peak of Gd2O3@PCD and Dotarem with the values of 2.21 ± 0.06 and 0.40 ± 0.004 for lymph node and 2.54 ± 0.04 and 1.21 ± 0.007 for the tumor, respectively. Furthermore, the lumbar-aortic lymph node is weakly visible in the original coronal image. In conclusion, the use of Gd2O3@PCD nanoparticles as novel MRMI CAs enables high resolution for the detection of lymph node metastasis in mice with the potential capability for breast cancer diagnostic imaging.

Functional roles of magnetic nanoparticles for the identification of metastatic lymph nodes in cancer patients

“…After labeling with NIR Cy5.5fluorophore, Gd-G6 provided real-time intraoperative guidance for surgical SLN resection under MR and NIR imaging conditions [ 96 ]. Another two signal-enhanced and high-resolution Gd-based MRI agents, Gd 2 O 3 @PCD [ 97 ] and Gd 3+ ·DOTA⊂SNPs [ 98 ] were successfully developed for the biological application of in vivo imaging. These injections of these two agents exhibited a crucial capacity for staging and diagnosing LNs and metastatic spread in tumor mice.…”

Kinetically inert manganese (II)-based hybrid micellar complexes for magnetic resonance imaging of lymph node metastasis

“…Magnetic resonance imaging (MRI) is a promising method for preoperative LN staging, because of its higher contrast of soft tissue than computed tomography, absence of radiation and superior resolution and depth of penetration than fluorescence imaging. However, the lack of sensitivity has limited MRI to stage LNs, and the use of contrast agents could help to improve this ability [ 14 , 15 ].…”