In vivo simultaneous SPECT-MR imaging of therapeutically engineered stem cells

Objectives: Stem cell (SC)-based therapies are promising targeted therapies with the potential to deliver a therapeutic payload directly to the primary tumors and metastatic lesions. Unfortunately, the precise mechanism governing the tumor-tropic properties and the delivery process of SCs is not fully understood, mainly because in vivo imaging of SC-based therapeutics is still inadequate. Therefore, the development of a sensitive, high resolution and non-invasive imaging tracking system is critical and strongly requested [1]. In our lab, we have developed an ultrahigh resolution MR-compatible small-animal SPECT system, the MRC-SPECT-I system for simultaneous SPECT-MR imaging small lab animals and the preliminary evaluation has been discussed in [2][3]. In this work, we will focus on quantitatively evaluating the MRC-SPECT-I performance in in vivo monitoring the migration and the fate of therapeutically engineered neural stem cells administrated in a mouse brain.

Methods: The MRC-SPECT-1 system consists of ten CdTe imaging detector modules assembled in a compact ring with a distance of 156 mm between the surfaces of two opposite detectors (Fig.1-A). Each detector has four CdTe detector hybrids having each one 64 × 32 pixels of 350 μm × 350 μm pitch size for an overall dimension of 22.5× 11.2 × 2 mm³ with four bump-bonded 2048-channel readout ASICs. Each detector is coupled with four 300- or 500-μm diameter pinholes. The SPECT detector ring is installed in a one-piece non-metal gantry with an outer diameter of 25 cm. The system is fully customized for operation inside MR scanners (Fig.1-B) as well as stand-alone platform. A precise system response function is derived using a new fine scanning technique and 390 system parameters are calibrated. The system spatial resolution is evaluated with a lab made miniaturized Jaszak phantom filled with 1.5mCi of Tc99m. The phantom has four sets of hot rods, with diameters of 1000μm, 750μm, 500μm and 350μm. We carried out the first simultaneous MRC-SPECT/MR imaging study of 111-In radiolabeled Neural Stem Cells (111In-NSCs) injected in the left and right hemisphere of a mouse brain (3.05 and 0.4 μCi, respectively). The imaging time was 1 hour and SPECT data were acquired 5 minutes per frame. We will further explore the potential of the MRC-SPECT-I system for in vivo detection and localization of radiolabeled NSCs in a brain tumor model. After administration of small populations of 111In-NSCs, the mouse will be imaged with the MRC-SPECT-I system at different time points to access the potential migration and the fate of NSCs in the brain tumor. In this study, we will quantitatively verify the sensitivity of the MRC-SPECT-I system for visualizing small number of NSCs under in vivo settings.

Results: We have evaluated the MRC-SPECT-I system for simultaneous SPECT-MR imaging in a resolution phantom and in a mouse brain. Fig. 1-C is a SPECT image of the resolution phantom acquired inside a Siemens Trio 3-T MR scanner, in which the 500 μm features can be clearly resolved. In 111In-NSC imaging study, we are able to resolve both the cell hot spots using 1-hour, 10-minute, and 5-minute data (Fig.1-F). Fig. 1-D shows simultaneous SPECT/MR images, while Fig. 1-E shows co-registered sequential SPECT and MR images of the same animal. In this case, the 14.1T MR scanner provided exquisite soft tissue contrast along with a spatial resolution of around 25 μm. Further imaging results will be discussed in this presentation.

Conclusion: Our preliminary results have shown that the MRC-SPECT-I system can readily detect and localize small populations of radiolabeled NSCs. This new study would allow us to quantify the potential impact of the MRC-SPECT-I system for in vivo monitoring of therapeutically engineered NSCs and for better understanding the NSC migration kinetics. Research Support: