Evaluation of safety and efficacy of adipose-derived stem cells in rat myocardial infarction model using hexadecyl-4-[¹²4I]iodobenzoate for cell tracking.

This study was aimed to evaluate the effect of (124)I-labeling with hexadecyl-4-iodobenzoate (HIB) on gene expression related to cell cycle, DNA repair, transcription, proliferation and differentiation of adipose-derived stem cells (ADSCs). [(124)I]HIB showed high labeling efficiency with ADSCs (51.3±1.3%, 0.3-2.0 Bq/cell) and there is no morphological change of ADSCs. In the microarray analysis of gene expression pattern, differences were not observed between non-labeled and [(124)I]HIB-labeled ADSCs. We demonstrated that (124)I-labeling with HIB did not affect the biological properties of ADSCs.

Fluorine-19 Labeling of Stromal Vascular Fraction Cells for Clinical Imaging Applications.

UNLABELLED: Stromal vascular fraction (SVF) cells are used clinically for various therapeutic targets. The location and persistence of engrafted SVF cells are important parameters for determining treatment failure versus success. We used the GID SVF-1 platform and a clinical protocol to harvest and label SVF cells with the fluorinated ((19)F) agent CS-1000 as part of a first-in-human phase I trial (clinicaltrials.gov identifier NCT02035085) to track SVF cells with magnetic resonance imaging during treatment of radiation-induced fibrosis in breast cancer patients. Flow cytometry revealed that SVF cells consisted of 25.0% ± 15.8% CD45+, 24.6% ± 12.5% CD34+, and 7.5% ± 3.3% CD31+ cells, with 2.1 ± 0.7 × 105 cells per cubic centimeter of adipose tissue obtained. Fluorescent CS-1000 (CS-ATM DM Green) labeled 87.0% ± 13.5% of CD34+ progenitor cells compared with 47.8% ± 18.5% of hematopoietic CD45+ cells, with an average of 2.8 ± 2.0 × 10¹² ¹9F atoms per cell, determined using nuclear magnetic resonance spectroscopy. The vast majority (92.7% ± 5.0%) of CD31+ cells were also labeled, although most coexpressed CD34. Only 16% ± 22.3% of CD45-/CD31-/CD34- (triple-negative) cells were labeled with CS-ATM DM Green. After induction of cell death by either apoptosis or necrosis, >95% of ¹9F was released from the cells, indicating that fluorine retention can be used as a surrogate marker for cell survival. Labeled-SVF cells engrafted in a silicone breast phantom could be visualized with a clinical 3-Tesla magnetic resonance imaging scanner at a sensitivity of approximately 2 × 106 cells at a depth of 5 mm. The current protocol can be used to image transplanted SVF cells at clinically relevant cell concentrations in patients. SIGNIFICANCE: Stromal vascular fraction (SVF) cells harvested from adipose tissue offer great promise in regenerative medicine, but methods to track such cell therapies are needed to ensure correct administration and monitor survival. A clinical protocol was developed to harvest and label SVF cells with the fluorinated (¹9F) agent CS-1000, allowing cells to be tracked with (19)F magnetic resonance imaging (MRI). Flow cytometry evaluation revealed heterogeneous ¹9F uptake in SVF cells, confirming the need for careful characterization. The proposed protocol resulted in sufficient ¹9F uptake to allow imaging using a clinical MRI scanner with point-of-care processing.

Stem Cell Labeling with Superparamagnetic Iron Oxide Nanoparticles Using Focused Ultrasound and Magnetic Resonance Imaging Tracking.

Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a "closed" MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labeling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs) were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43 ± 9.55 nm) had the highest T2 relaxivity (136.62 Fe mM(-1) S(-1)) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally, confirmed by histological evaluation, pronounced signal attenuation on T2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the "closed" device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking.

Low-Intensity Pulsed Ultrasound Improves the Functional Properties of Cardiac Mesoangioblasts.

Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5'-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of ß1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy.

Adenovirus-mediated expression of human sodium-iodide symporter gene permits in vivo tracking of adipose tissue-derived stem cells in a canine myocardial infarction model.

INTRODUCTION: In vivo tracking of the transplanted stem cells is important in pre-clinical research of stem cell therapy for myocardial infarction. We examined the feasibility of adenovirus-mediated sodium iodide symporter (NIS) gene to cell tracking imaging of transplanted stem cells in a canine infarcted myocardium by clinical single photon emission computed tomography (SPECT). METHODS: Beagle dogs were injected intramyocardially with NIS-expressing adenovirus-transfected canine stem cells (Ad-hNIS-canine ADSCs) a week after myocardial infarction (MI) development. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and (99m)Tc-pertechnetate ((99m)TcO4(-)) SPECT imaging were performed for assessment of infarcted myocardium and viable stem cell tracking. Transthoracic echocardiography was performed to monitor any functional cardiac changes. RESULTS: Left ventricular ejection fraction (LVEF) was decreased after LAD ligation. There was no significant difference in EF between the groups with the stem cell or saline injection. (125)I uptake was higher in Ad-hNIS-canine ADSCs than in non-transfected ADSCs. Cell proliferation and differentiation were not affected by hNIS-carrying adenovirus transfection. (99m)Tc-MIBI myocardial SPECT imaging showed decreased radiotracer uptake in the infarcted apex and mid-anterolateral regions. Ad-hNIS-canine ADSCs were identified as a region of focally increased (99m)TcO4(-) uptake at the lateral wall and around the apex of the left ventricle, peaked at 2 days and was observed until day 9. CONCLUSIONS: Combination of adenovirus-mediated NIS gene transfection and clinical nuclear imaging modalities enables to trace the fate of transplanted stem cells in infarcted myocardium for translational in vivo cell tracking study for prolonged duration.

Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-¹²4I-iodobenzoate in rat myocardial infarction model.

This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via the hexadecyl-4-(124)I-iodobenzoate ((124)I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with (124)I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of (124)I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by (124)I-HIB labeling. In vivo tracking of the (124)I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, (124)I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials.

Radiopharmaceutical stem cell tracking for neurological diseases.

Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases.

Differentiation of neural stem/progenitor cells using low-intensity ultrasound.

Herein, we report the evaluation of apoptosis, cell differentiation, neurite outgrowth and differentiation of neural stem/progenitor cells (NSPCs) in response to low-intensity ultrasound (LIUS) exposure. NSPCs were cultured under different conditions, with and without LIUS exposure, to evaluate the single and complex effects of LIUS. A lactic dehydrogenase assay revealed that the cell viability of NSPCs was maintained with LIUS exposure at an intensity range from 100 to 500 mW/cm(2). Additionally, in comparison with no LIUS exposure, the cell survival rate was improved with the combination of medium supplemented with nerve growth factor and LIUS exposure. Our results indicate that LIUS exposure promoted NSPC attachment and differentiation on a glass substrate. Neurite outgrowth assays revealed the generation of longer, thicker neurites after LIUS exposure. Furthermore, LIUS stimulation substantially increased the percentage of differentiating neural cells in NSPCs treated with nerve growth factor in comparison with the unstimulated group. The high percentage of differentiated neural cells indicated that LIUS induced neuronal networks denser than those observed in the unstimulated groups. Furthermore, the release of nitric oxide, an important small-molecule neurotransmitter, was significantly upregulated after LIUS exposure. It is therefore reasonable to suggest that LIUS promotes the differentiation of NSPCs into neural cells, induces neurite outgrowth and regulates nitric oxide production; thus, LIUS may be a potential candidate for NSPC induction and neural cell therapy.

From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects.

Tissue engineering offers enormous potential for bone regeneration. Despite extensive in vitro and in vivo work, few strategies translate into clinical practice. This paper describes the combination of skeletal stem cells (SSCs) and impaction bone grafting (IBG) for the treatment of patients with bone defects associated with avascular necrosis of the femoral head. SSCs and milled allograft were impacted into necrotic bone in the femoral heads of four patients. Three patients remained asymptomatic at 22-44 month follow-up, but one patient has required total hip replacement (both hips). This has allowed retrieval of the femoral heads, which were analysed structurally and functionally by µCT, histology and mechanical testing. A central channel of impacted bone was found in the femoral heads, which displayed a mature trabecular micro-architecture. The impacted bone was denser than the surrounding trabecular bone, as strong in compression and with histological micro-architecture comparable to that of trabecular bone. Analysis of the retrieved femoral head samples has demonstrated that this tissue-engineering strategy regenerates bone that is both structurally and functionally analogous to normal trabecular bone. SSCs, together with IBG, have proved an effective treatment for avascular necrosis of the femoral head and offer significant potential for the broader spectrum of bone defects.

Effect of transplantation route on stem cell migration to fibrotic liver of rats via cellular magnetic resonance imaging.

BACKGROUND AIMS: Assessing mesenchymal stromal cells (MSCs) after grafting is essential for understanding their migration and differentiation processes. The present study sought to evaluate via cellular magnetic resonance imaging (MRI) if transplantation route may have an effect on MSCs engrafting to fibrotic liver of rats. METHODS: Rat MSCs were prepared, labeled with superparamagnetic iron oxide and scanned with MRI. Labeled MSCs were transplanted via the portal vein or vena caudalis to rats with hepatic fibrosis. MRI was performed in vitro before and after transplantation. Histologic examination was performed. MRI scan and imaging parameter optimization in vitro and migration under in vivo conditions were demonstrated. RESULTS: Strong MRI susceptibility effects could be found on gradient echo-weighted, or T2∗-weighted, imaging sequences from 24 h after labeling to passage 4 of labeled MSCs in vitro. In vivo, MRI findings of the portal vein group indicated lower signal in liver on single shot fast spin echo-weighted, or T2-weighted, imaging and T2∗-weighted imaging sequences. The low liver MRI signal increased gradually from 0-3 h and decreased gradually from 3 h to 14 days post-transplantation. The distribution pattern of labeled MSCs in liver histologic sections was identical to that of MRI signal. It was difficult to find MSCs in tissues near the portal area on day 14 after transplantation; labeled MSCs appeared in fibrous tuberculum at the edge of the liver. No MRI signal change and a positive histologic examination were observed in the vena caudalis group. CONCLUSIONS: The portal vein route seemed to be more beneficial than the vena caudalis on MSC migration to fibrotic liver of rats via MRI.

Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications.

Stem cells are promising therapeutics for cardiovascular diseases, and i.v. injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemoattractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (pFUS), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemoattractant expression in pFUS-treated tissue prior to cell infusions. We demonstrate that pFUS is nondestructive to murine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate that local upregulation of chemoattractants in pFUS-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when pFUS treatments and cell infusions were repeated daily. This study demonstrates that pFUS defines transient "molecular zip codes" of elevated chemoattractants in targeted muscle tissue, which effectively provides spatiotemporal control and tunability of the homing process for multiple stem cell types. pFUS is a clinically translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases.

Molecular imaging and tracking stem cells in neurosciences.

Stem cell transplantation is a promising new therapeutic option in different neurological diseases. However, it is not yet possible to translate its potential from animal models to clinical application. One of the main problems of applying stem cell transplantation in clinical medium is the difficulty of detection, localization, and examination of the stem cells in vivo at both cellular and molecular levels. State-of-the-art molecular imaging techniques provide new and better means for noninvasive, repeated, and quantitative tracking of stem cell implant or transplant. From initial deposition to the survival, migration, and differentiation of the transplant/implanted stem cells, current molecular imaging methods allow monitoring of the infused cells in the same live recipient over time. The present review briefly summarizes and compares these molecular imaging methods for cell labeling and imaging in animal models as well as in clinical application and sheds light on consecutive new therapeutic options if appropriate.

Superparamagnetic iron oxide is suitable to label tendon stem cells and track them in vivo with MR imaging.

Tendon stem cells (TSCs) may be used to effectively repair or regenerate injured tendons. However, the fates of TSCs once implanted in vivo remain unclear. This study was aimed to determine the feasibility of labeling TSCs with super-paramagnetic iron oxide (SPIO) nano-particles to track TSCs in vivo using MRI. Rabbit TSCs were labeled by incubation with 50 µg/mL SPIO. Labeling efficiency, cell viability, and proliferation were then measured, and the stemness of TSCs was tested by quantitative real time RT-PCR (qRT-PCR) and immunocytochemistry. We found that the labeling efficiency of TSCs reached as high as 98%, and that labeling at 50 µg/mL SPIO concentrations did not alter cell viability and cell proliferation compared to non-labeled control cells. Moreover, the expression levels of stem cell markers (Nucleostemin, Nanog, and Oct-4) did not change in SPIO-labeled TSCs compared to non-labeled cells. Both labeled and non-labeled cells also exhibited similar differentiation potential. Finally, labeled TSCs could be detected by MRI both in vitro and in vivo. Taken together, the findings of this study show that labeling TSCs with SPIO particles is a feasible approach to track TSCs in vivo by MRI, which offers a non-invasive method to monitor repair of injured tendons.

In vivo cell tracking via ¹8F-fluorodeoxyglucose labeling: a review of the preclinical and clinical applications in cell-based diagnosis and therapy.

The rising interest in using functional cells for diagnosis and treatment has created an urgent need for in vivo cell-tracking techniques. Certain advanced techniques, such as those involving reporter genes or nanoparticles, are still awaiting confirmation of their safety and feasibility in human patients. Tracking cells by labeling them with (18)F-fluorodeoxyglucose, a tracer clinically used in positron emission tomography (PET), may be one way to rapidly translate some of these principles from bench to bedside. The preliminary results are exciting, although further development, optimization, and validation are required. Here, several applications of the technique are surveyed: finding inflammatory foci, targeting cancer immunotherapies, tracking transplanted islet cells, and monitoring cardiac stem cells. Advantages, limitations, and prospects of the technique are discussed. These early experiences only highlight the existing need to improve cell-labeling techniques using PET tracers. This method may finally lead to the development of effective and convenient methods for clinical cell-tracking techniques involving PET/computed tomography.

Stem cell tracking: toward clinical application in oncology?

Noninvasive cellular imaging allows the tracking of grafted cells as well as the monitoring of their migration, suggesting potential applications to track both cancer and therapeutic stem cells. Cell tracking can be performed by two approaches: direct labeling (cells are labeled with tags) and indirect labeling (cells are transfected with a reporter gene and visualized after administration of a reporter probe). Techniques for in vivo detection of grafted cells include optic imaging, nuclear medicine imaging, magnetic resonance imaging, microCT imaging and ultrasound imaging. The ideal imaging modality would bring together high sensitivity, high resolution and low toxicity. All of the available imaging methods are based on different principles, have different properties and different limitations, so several of them can be considered complementary. Transfer of these preclinical cellular imaging modalities to stem cells has already been reported, and transfer to clinical practice within the next years can be reasonably considered.

In search of an efficient injection technique for future clinical application of spermatogonial stem cell transplantation: infusion of contrast dyes in isolated cadaveric human testes.

OBJECTIVE: To develop an efficient infusion technique for human spermatogonial stem cell transplantation. DESIGN: A mixture with ultrasonic contrast, computerized tomography (CT) contrast, and Chinese ink was injected into isolated human testes through different sites (the rete testis, the head of the epididymis, the deferent duct, and blind testicular infusion). Ultrasound transducer was used to visualize the injection site and to observe the flow of the mixture injected in the testes. Then, micro-CT scan was used to construct three-dimensional images, allowing the calculation of the testicular volume filled by the mixture. Finally the efficiency of the infusion was evaluated on histologic sections. SETTING: Research laboratory. PATIENT(S): Cadaver testes obtained from autopsied bodies at the department of pathology. INTERVENTION(S): Ultrasound-guided infusion of contrast liquid. MAIN OUTCOME MEASURE(S): Contrast liquid-filled testis volume and presence of ink in seminiferous tubules. RESULT(S): Ultrasonography clearly visualized the flow when seminiferous tubules were injected from the rete testis. No flow was observed when infusions were made either blindly, into the deferent duct, or into the head of the epididymis. On micro-CT no significant differences were observed between the different volumes. After rete testis infusion, ink particles were found in the lumen of the rete testis and in tubules, close and distant from the rete testis. CONCLUSION(S): A single ultrasound-guided injection of 800 µL in the rete testis may provide a promising method to transplant human spermatogonial stem cells in a clinical setting.

(18)F-FDG cell labeling may underestimate transplanted cell homing: more accurate, efficient, and stable cell labeling with hexadecyl-4-[(18)F]fluorobenzoate for in vivo tracking of transplanted human progenitor cells by positron emission tomography.

Cell therapy is expected to restore perfusion and improve function in the ischemic/infarcted myocardium; however, the biological mechanisms and local effects of transplanted cells remain unclear. To assess cell fate in vivo, hexadecyl-4-[(18)F]fluorobenzoate ((18)F-HFB) cell labeling was evaluated for tracking human circulating progenitor cells (CPCs) with positron emission tomography (PET) and was compared to the commonly used 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)F-FDG) labeling method in a rat myocardial infarction model. CPCs were labeled with 18F-HFB or (18)F-FDG ex vivo under the same conditions. (18)F-HFB cell-labeling efficiency (23.4 ± 7.5%) and stability (4 h, 88.4 ± 6.0%) were superior to (18)F-FDG (7.6 ± 4.1% and 26.6 ± 6.1%, respectively; p < 0.05). Neither labeling approach significantly altered cell viability, phenotype or migration potential up to 24 h postlabeling. Two weeks after left anterior descending coronary artery ligation, rats received echo-guided intramyocardial injection in the infarct border zone with (18)F-HFB-CPCs, (18)F-FDG-CPCs, (18)F-HFB, or (18)F-FDG. Dynamic PET imaging of both (18)F-HFB-CPCs and(18)F-FDG-CPCs demonstrated that only 16-37% of the initial injection dose (ID) was retained in the injection site at 10 min postdelivery, and remaining activity fell significantly over the first 4 h posttransplantation. The (18)F-HFB-CPC signal in the target area at 2 h (23.7 ± 14.7% ID/g) and 4 h (17.6 ± 13.3% ID/g) postinjection was greater than that of (18)F-FDG-CPCs (5.4 ± 2.3% ID/g and 2.6 ± 0.7% ID/g, respectively;p < 0.05). Tissue biodistribution confirmed the higher radioactivity in the border zone of (18)F-HFB-CPC rats. Immunostaining of heart tissue sections revealed no significant difference in cell retention between two labeled cell transplantation groups. Good correlation with biodistribution results was observed in the (18)F-HFB-CPC rats (r = 0.81, p < 0.05). Compared to (18)F-FDG, labeling human CPCs with(18)F-HFB provides a more efficient, stable, and accurate way to quantify the distribution of transplanted cells. (18)F-HFB cell labeling with PET imaging offers a better modality to enhance our understanding of early retention, homing, and engraftment with cardiac cell therapy.

Bone marrow stem cell adherence into old anterior myocardial infarction: a scintigraphic study using Tl-201 and Tc-99m-HMPAO.

AIM: The precise localization of bone marrow stem cells (SCs) into the necrotic tissue after intracoronary infusion (ICI) may be important for the therapeutic outcome. This study aims to examine the correlation between Tl-201 and Tc-99m-hexa-methyl-propylene-amine-oxime (HMPAO) images. METHODS: Thirteen patients, aged 36-62 years, with an old, nonviable, anterior myocardial infarction (MI) and reduced myocardial contractility (LVEF <40%), underwent ICI of selected CD133(+) and CD133(neg)CD34(+) SCs. One hour after the ICI, SPECT imaging with Tc-99m-HMPAO was performed in all patients and the acquired images were compared with the images obtained during the initial imaging for demonstration of viability (myocardial perfusion imaging with pharmacologic stress and Tl-201). Furthermore, two fused bull's eye images of Tc-99m-HMPAO and Tl-201 rest reinjection were created in six patients and regions of interest were set on Tl-201 and Tc-99m-HMPAO bull's eye images. RESULTS: The comparison of the two sets of images revealed an intense accumulation of the SCs in the infarcted area with absence of viability as assessed by Tl-201 reinjection images. In the subset of patients in whom fused bull's eye images were produced, the comparison demonstrated that the percentage of the infarcted area with SCs' adherence was 83.2 ± 17%. CONCLUSIONS: Tl-201 images are complementary with the respective Tc-99m-HMPAO ones, revealing a precise localization of SCs in the infarcted area. Tc-99m-HMPAO labeling of SCs is a reliable method for cell monitoring after ICI in nonviable myocardium after an anterior MI.

Molecular imaging for stem cell transplantation in neuroregenerative medicine.

Stem cell transplantation is a promising new therapeutic option in different neurological diseases. However, it was not yet possible to translate its potential from animal models to clinical application. One of the main problems of applying stem cell transplantation in clinical medium is the difficulty of detection, localization, and examination of the stem cells in vivo at both cellular and molecular levels. State-of-the-art molecular imaging techniques provide new and better means for noninvasive, repeated, and quantitative tracking of stem cell implant or transplant. From initial deposition to the survival, migration, and differentiation of the transplant/implanted stem cells, current molecular imaging methods allow monitoring of the infused cells in the same live recipient over time. The present review briefly summarizes and compares these molecular imaging methods for cell labeling and imaging in animal models as well as in clinical application and sheds light on consecutive new therapeutic options if appropriate.