Feasibility of Monitoring Tumor Response by Tracking Nanoparticle-Labelled T Cells Using X-ray Fluorescence Imaging-A Numerical Study

Int J Mol Sci. 2021 Aug 14;22(16):8736. doi: 10.3390/ijms22168736.

Abstract

Immunotherapy has been a breakthrough in cancer treatment, yet only a subgroup of patients responds to these novel drugs. Parameters such as cytotoxic T-cell infiltration into the tumor have been proposed for the early evaluation and prediction of therapeutic response, demanded for non-invasive, sensitive and longitudinal imaging. We have evaluated the feasibility of X-ray fluorescence imaging (XFI) to track immune cells and thus monitor the immune response. For that, we have performed Monte Carlo simulations using a mouse voxel model. Spherical targets, enriched with gold or palladium fluorescence agents, were positioned within the model and imaged using a monochromatic photon beam of 53 or 85 keV. Based on our simulation results, XFI may detect as few as 730 to 2400 T cells labelled with 195 pg gold each when imaging subcutaneous tumors in mice, with a spatial resolution of 1 mm. However, the detection threshold is influenced by the depth of the tumor as surrounding tissue increases scattering and absorption, especially when utilizing palladium imaging agents with low-energy characteristic fluorescence photons. Further evaluation and conduction of in vivo animal experiments will be required to validate and advance these promising results.

Keywords: T cell; X-ray fluorescence imaging; XFI; gold; immunotherapy; nanoparticles; palladium; simulation.

MeSH terms

  • Animals
  • Computer Simulation*
  • Feasibility Studies
  • Fluorescence
  • Gold
  • Immunotherapy*
  • Male
  • Metal Nanoparticles*
  • Mice
  • Mice, Nude
  • Monte Carlo Method
  • Neoplasms / diagnostic imaging*
  • Neoplasms / therapy
  • Optical Imaging / methods*
  • Palladium
  • Tomography, X-Ray Computed / methods*

Substances

  • Palladium
  • Gold