Melanie Kimm, Presenter: Nothing to Disclose

Reinhard Meier MD, PhD, Abstract Co-Author: Nothing to Disclose

Ernst J. Rummeny MD, Abstract Co-Author: Nothing to Disclose

Vasilis Ntziachristos PhD, Abstract Co-Author: Stockholder, iThera Medical GmbH

Stratis Tzoumas, Abstract Co-Author: Nothing to Disclose

Marcus Settles PhD, Abstract Co-Author: Nothing to Disclose

To track tumor-specific T cells to tumors and visualize their biodistribution with MRI and multispectral optoacoustic tomography (MSOT).

CD8+ T cells expressing a T cell receptor specific for an ovalbumin peptide were used for the adoptive transfer. Tumors were introduced by murine lymphoma cell lines. Before transfer, T cells were labeled with iron nanoparticles or near infrared dyes. Labeling efficiencies were evaluated with phantom studies, IHC and IF/darkfield microscopy, respectively. Cell viability and functionality was analysed by flow cytometry, MTT and ELISA studies. Monitoring was performed with a MRI system (3T, Philips, Germany) and MSOT (iTheraMedical, Germany) at day 3 after adoptive transfer.

Cell viability and survival is depending on the concentration and incubation conditions (e.g. time, temperature) of the contrast agent. By optimizing the protocols, we reach over 80% cell survival with no difference in functionality compared to unlabeled control T cells. Phantom studies revealed the visualisation of as little as 100.000 cells by MRI and 1.000 cells by MSOT, respectively. In vivo analysis showed that transfered labeled T cells accumulate at the tumor site and in peripheral lymphoid organs (spleen, lymph nodes).

Tumor-reactive T cells can be intracellularly labeled with iron nanoparticles and near infrared dyes at concentrations that do not harm the cells. At these conditions cells can be identified by using MRI and MSOT. Not only the tumor homing can be followed but also the biodistribution of the cells can be monitored.

Tracking of cytotoxic T lymphocytes with non-invasive imaging techniques such as MRI and MSOT is feasible and may lead to a better understanding of the biodistribution of transfered T cells for a rapid identification of responding patients shortly after the adoptive transfer.

Kimm, M, Meier, R, Rummeny, E, Ntziachristos, V, Tzoumas, S, Settles, M, Tracking of Tumor-specific T Cells by MR Imaging and Multispectral Optoacoustic Tomography (MSOT).  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14005565.html