Characterisation of multimodal contrast agents for lymph node imaging

Adam, G., Denisov, V., Rattray, Z., Thomson, A., Moug, S., Jansson, T., Farrington, S., Moran, C. and Mulvana, H. (2023) Characterisation of multimodal contrast agents for lymph node imaging. Leeds Microbubble Symposium 2023: From Fundamentals to Application, Leeds, UK, 17-19 Jul 2023.

Abstract

Contrast-enhanced magnetomotive ultrasound (CE-MMUS) aims to combine two forms of contrast agents, superparamagnetic iron oxide nanoparticles (SPIONS) and microbubbles (MBs), to improve early detection of lymph node metastasis in colorectal cancer. Simulation studies indicate SPIONMBs may yield larger tissue displacements than SPIONS alone, improving sensitivity to metastatic stiffness. We present detailed characterisation of each agent alongside tissue mimicking material (TMM) validation studies utilising a catalyst polymerising hydrogel to trap both MBs and SPIONs for detailed investigation. Target-ready (TR) MBs (MicroMarker, Fujifilm Visualsonics) with streptavidin binding sites were reconstituted (3 x 109 MBs/mL) and added to biotinylated SPIONs to create SPION-MBs. Concentration, polydispersity, mean diameter and verification of SPION loading were obtained with nanoparticle tracking analysis (NTA). Mean SPION loading per MB was further validated through titration and nuclear magnetic resonance spectroscopy (1H NMR; Agilent/Varian VNMR-S, 500MHz). Polyacrylamide (PAAm) hydrogel inclusions (θ 5 mm x 12.5 mm) of each agent (0.6mg/ml SPIONS ± 50µL of TR-MBs or SPIONS + saline), held in PVA cubes (25 mm3) were subject to alternating magnetic field (0.14T, 4 & 20 Hz) and imaged (Vevo 3100, 40 MHz). RF signals were post processed in MATLAB to recover MMUS displacement. Successful conjugation of SPIONs to MBs was confirmed when over 90% of particles had diameter 1385 nm, without free SPIONs detected. 1H NMR spectroscopy of biotinylated SPIONs added in increasing ratios to TR-MBs established T2 relaxation time to determine maximum loading capacity showing saturation at 1:3. Knowing the ratio of these two contrast agents is vital to ensure complete conjugation of all the SPIONS to the MM before fabrication and incorporation in the TMM material. PAAm hydrogel was fabricated and preliminary data shows the displacement values for the PAAm containing SPIONsB or SPIONs-B + TR-MM. It can be noted that SPIONs-B + TR-MM display a trend towards higher displacement especially for the 20Hz case, though further investigation is required for optimisation and progression to preclinical work.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mulvana, Dr Helen
• Authors: Adam, G., Denisov, V., Rattray, Z., Thomson, A., Moug, S., Jansson, T., Farrington, S., Moran, C., and Mulvana, H.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: International Leeds Microbubble Symposium, Leeds, United Kingdom, 17/07/23

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