Assessment of three techniques for delivering stem cells to the heart using PET and MR imaging.

BACKGROUND: Stem cell therapy has a promising potential for the curing of various degenerative diseases, including congestive heart failure (CHF). In this study, we determined the efficacy of different delivery methods for stem cell administration to the heart for the treatment of CHF. Both positron emission tomography (PET) and magnetic resonance imaging (MRI) were utilized to assess the distribution of delivered stem cells. METHODS: Adipose-derived stem cells of male rats were labeled with super-paramagnetic iron oxide (SPIO) and 18 F-fluorodeoxyglucose (FDG). The left anterior descending coronary artery (LAD) of the female rats was occluded to induce acute ischemic myocardial injury. Immediately after the LAD occlusion, the double-labeled stem cells were injected into the ischemic myocardium (n = 5), left ventricle (n = 5), or tail vein (n = 4). In another group of animals (n = 3), the stem cells were injected directly into the infarct rim 1 week after the LAD occlusion. Whole-body PET images and MR images were acquired to determine biodistribution of the stem cells. After the imaging, the animals were euthanized and retention of the stem cells in the vital organs was determined by measuring the cDNA specific to the Y chromosome. RESULTS: PET images showed that retention of the stem cells in the ischemic myocardium was dependent on the cell delivery method. The tail vein injection resulted in the least cell retention in the heart (1.2% ± 0.6% of total injected cells). Left ventricle injection led to 3.5% ± 0.9% cell retention and direct myocardial injection resulted in the highest rate of cell retention (14% ± 4%) in the heart. In the animals treated 1 week after the LAD occlusion, rate of cell retention in the heart was only 4.5% ±1.1%, suggesting that tissue injury has a negative impact on cell homing. In addition, there was a good agreement between the results obtained through PET-MR imaging and histochemical measurements. CONCLUSION: PET-MR imaging is a reliable technique for noninvasive tracking of implanted stem cells in vivo. Direct injection of stem cells into the myocardium is the most effective way for cell transplantation to the heart in heart failure models.

NEMA NU 4-2008 comparison of preclinical PET imaging systems.

UNLABELLED: The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. METHODS: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. RESULTS: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. CONCLUSION: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer.

PURPOSE: Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, (18)F-fluoro-2-deoxy-D: -glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs. METHODS: Samples of 10(5) ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed. RESULTS: Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns. CONCLUSION: For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.

On the significance of defective block detectors in clinical (18)F-FDG PET/CT imaging.

INTRODUCTION: Clinical positron emission tomography (PET) systems based on block detector designs suffer occasional block detector failures, which can result in patient scan cancelations. In this study, we examine the effect of defective block detectors on measurements of maximum standard uptake value (SUV(max)) and clinical image quality in 3D 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) PET/computed tomography (CT) imaging. METHODS: A Data Spectrum anthropomorphic torso phantom (4.7 kBq/ml FDG concentration, defined as SUV of 1.0) was imaged in a normally functioning Siemens Biograph 16 HiRez PET/CT scanner using a whole-body imaging protocol. Spherical lesions with SUVs ranging from 10.0 to 13.5 were placed in the phantom. Defective block detectors were simulated by zeroing the appropriate lines of response in the sinograms. Eleven one-block and seventeen two-block defect configurations were simulated in the phantom sinograms. The images were reconstructed, and the measured SUV(max) was compared with the SUV(max) for the images without detector defects. Twelve clinical PET scans were evaluated before and after simulated detector defects cases ranging from a single block up to 12 blocks (bucket). The reconstructed images were independently scored for image quality and clinical diagnosis by two nuclear physicians blinded to the presence and severity of defects in the images. RESULTS: The mean change in phantom SUV(max) was -2% (range, -6% to +3%) in the presence of a single defective block detector and -3% (range, -11% to +7%) in the presence of two defective block detectors, respectively. For the clinical patient studies, there was no significant decline in image quality score from one to two defective block detectors. In the case of 3-4 defective block detectors, image quality became marginal, and image degradation was significant with a defective bucket (12 blocks). CONCLUSION: For one or two defective block detectors in a 3D PET camera, while waiting for the repair service, routine patient scans can proceed with the proviso that the reading physician is made aware of the detector failure.