Characterisation of multimodal contrast agents for Contrast Enhanced Magnetomotive Ultrasound to stage colorectal cancer

Adam, G., Densiov, V., Rattray, Z., Thomson, A., Moug, S., Jansson, T., Farrington, S., Moran, C. M. and Mulvana, H. (2023) Characterisation of multimodal contrast agents for Contrast Enhanced Magnetomotive Ultrasound to stage colorectal cancer. SINAPSE 15th Annual Scientific Meeting, Glasgow, UK, 14 Jun 2023.

Abstract

Background, Motivation and Objective: Contrast-Enhanced Magneto Motive Ultrasound (CE-MMUS) is a novel ultrasound-based imaging modality combining two different contrast agents, Superparamagnetic Iron Oxide Particles (SPIONS) and Microbubbles (MBs) for tissue stiffness assessment. These Magnetic MBs can delineate lymph nodes through standard perfusion approaches aiming to yield larger tissue displacements for more sensitive stiffness interrogation to determine metastatic involvement. In this study, we present a thorough characterisation of each agent to establish sizing, polydispersity and most importantly SPION loading on the MBs. After particle characterisation, a novel MB-SPIONS loaded tissue mimicking material [1] was fabricated exhibiting an improved tissue displacement over SPIONS alone. Experimental Methods: Target ready MicroMarker (TR-MM, Fujifilm Visualsonics) pre-formulated to include streptavidin binding sites on the lipid shell, was reconstituted to yield 2 x 109 bubbles/vial. SPIONs were biotinylated (SPIONS-B) [2] and combined with the MBs to form SPION-MBs complexes. Detailed characterisation and verification of targeting was performed using Nanoparticle Tracking Analysis (NTA). Mean SPIONs-B loading per TR-MM microbubbles was calculated through titration and 1H NMR (Agilent/Varian VNMR-S 500MHz). Polyacrylamide (PAAm) hydrogel samples incorporating SPIONs or SPION-MBs were subject to an externally applied alternating magnetic field (0.14T, 4 & 20 Hz, sinusoid) and imaged with ultrasound (Vevo 3100). RF signals were post processed in Matlab to recover mean displacement. Results/Discussion: NTA measurements provided particle sizing, 66.9 ± 1.5nm for the SPIONS-B and 1100.0 ± 180.0nm for the TR-MM, but also confirmed successful conjugation of SPIONs-B to TRMM.1H NMR measurements of SPIONs-B to increasing TR-MM ratio was used to determine maximum loading of SPIONs that could be achieved per microbubble. T2 relaxation time of the proton peak was used for each dilution ratio as shown in (A). Data showed a gradual narrowing of the proton peak (increasing T2) to the point saturation occurs at a ratio of 1:3. PAAm hydrogel was fabricated and (B) shows preliminary data of displacement values. 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
• Additional Information: Funding: Cancer Research UK A23333.
• Keywords: multimodal contrast agents, colorectal cancer, Contrast Enhanced Magnetomotive Ultrasound
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mulvana, Dr Helen
• Authors: Adam, G., Densiov, V., Rattray, Z., Thomson, A., Moug, S., Jansson, T., Farrington, S., Moran, C. M., and Mulvana, H.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: SINAPSE Annual Scientific Meeting, Glasgow, United Kingdom, 20/06/23

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