Tumour-associated macrophages (TAM) are forced by cancer cells to adopt an anti-inflammatory phenotype and secrete factors to promote tumour invasion thus being responsible for poor patient outcome. The aim of this study is to develop a clinically applicable, non-invasive method to obtain a quantitative TAM detection in tumour tissue. The method is based on longitudinal proton relaxation rate (R1) measurements at low field (0.01–1 MHz) to assess the localization of ferumoxytol (clinical approved iron oxide particles) in TAM present in melanoma tumours, where R1 = 1/T1. R1 at low magnetic fields appears highly dependent on the intra or extra cellular localization of the nanoparticles thus allowing an unambiguous TAM quantification. R1 profiles were acquired on a Fast Field-Cycling relaxometer equipped with a 40 mm wide bore magnet and an 11 mm solenoid detection coil placed around the anatomical region of interest. The R1 values measured 3 h and 24 h after the injection were significantly different. At 24 h R1 exhibited a behavior similar to “in vitro” ferumoxytol-labelled J774A.1 macrophages whereas at 3 h, when the ferumoxytol distribution was extracellular, R1 exhibited higher values similar to that of free ferumoxytol in solution. This finding clearly indicated the intracellular localization of ferumoxytol at 24 h, as confirmed by histological analysis (Pearls and CD68 assays). This information could be hardly achievable from measurements at a single magnetic field and opens new horizons for cell tracking applications using FFC-MRI.
|Number of pages
|Early online date
|27 Jan 2020
|Published - 1 Apr 2020
The authors would like to acknowledge Dr Dana Dawson, University of Aberdeen, UK, for the supply of ferumoxytol.
This project has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”) and it was performed in the frame of the COST Action AC15209 (EURELAX). Maria Rosaria Ruggiero was supported by a “FIRC-AIRC fellowship for Italy”. The Italian Ministry for Education and Research (MIUR) is gratefully acknowledged for yearly FOE funding to the Euro-BioImaging Multi-Modal Molecular Imaging Italian Node (MMMI).
All data analysed during this study are included in this published article (and its supplementary information file). Other raw data required to reproduce these findings are available from the corresponding author on reasonable request.
- Iron oxide particles
- Low field relaxometry (NMRD)
- Intracellular water lifetime
- Tumour associated macrophages
- Magnetic resonance imaging