Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents.

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION-(64)Cu). This can now be potentially used for (64)Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR(+)SPION(pos) T cells effectively target in vitro CD19(+) lymphoma.

Frequency bandwidth extension by use of multiple Zeeman field offsets for electron spin-echo EPR oxygen imaging of large objects.

PURPOSE: Electron spin-echo (ESE) oxygen imaging is a new and evolving electron paramagnetic resonance (EPR) imaging (EPRI) modality that is useful for physiological in vivo applications, such as EPR oxygen imaging (EPROI), with potential application to imaging of multicentimeter objects as large as human tumors. A present limitation on the size of the object to be imaged at a given resolution is the frequency bandwidth of the system, since the location is encoded as a frequency offset in ESE imaging. The authors' aim in this study was to demonstrate the object size advantage of the multioffset bandwidth extension technique. METHODS: The multiple-stepped Zeeman field offset (or simply multi-B) technique was used for imaging of an 8.5-cm-long phantom containing a narrow single line triaryl methyl compound (trityl) solution at the 250 MHz imaging frequency. The image is compared to a standard single-field ESE image of the same phantom. RESULTS: For the phantom used in this study, transverse relaxation (T(2e)) electron spin-echo (ESE) images from multi-B acquisition are more uniform, contain less prominent artifacts, and have a better signal to noise ratio (SNR) compared to single-field T(2e) images. CONCLUSIONS: The multi-B method is suitable for imaging of samples whose physical size restricts the applicability of the conventional single-field ESE imaging technique.

Multiple-stepped Zeeman field offset method applied in acquiring enhanced resolution spin-echo electron paramagnetic resonance images.

PURPOSE: Electron paramagnetic resonance (EPR) imaging techniques provide quantitative in vivo oxygen distribution images. Time-domain techniques including electron spin echo (ESE) imaging have been under study in recent years for their robustness and promising new features. One of the limitations of ESE imaging addressed here is the finite acquisition frequency bandwidth, which imposes limits on applied magnetic field gradients and the resulting image spatial resolution. In order to improve the image spatial resolution, we have extended the effective frequency bandwidth of the imaging system by acquiring projections at multiple Zeeman magnetic field offsets and combining them to restore complete projections obtained with more uniform frequency response, resulting in higher quality images. METHODS: In multiple-stepped magnetic field or multi-B scheme, every projection of the three dimensional object is acquired at different main or Zeeman magnetic field (B) offset values. The data from field offset steps are combined, normalizing to the imaging system frequency acquisition window function, a sensitivity profile, to restore the complete projection. A multipurpose pulse EPR imager and phantoms containing the same type of spin probe (OX063H) used in routine animal imaging were also used in this study. RESULTS: Using the multi-B method, we were able to acquire images of our phantoms with enhanced spatial resolution compared to the conventional ESE approach. Compared to standard single-B ESE images, the T2 resolutions of multi-B images were superior using a high spatial-resolution regime. Image artifacts present in high-gradient single-B ESE images are also substantially reduced using in the multi-B scheme. CONCLUSIONS: The multi-B method is less susceptible to instrumental limitations for larger gradient fields and acquiring images with higher spatial resolution better overall quality, without the need to alter the existing pulse ESE image acquisition hardware.