A method for quantitative cell tracking using SPECT for the evaluation of myocardial stem cell therapy

Stodilka, Robert Z.; Blackwood, Kimberley J.; Kong, Huafu; Prato, Frank S.

doi:10.1097/01.mnm.0000237987.31597.cf

Cited by 21 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By labeling canine bone marrow mesenchymal cells with 111 In-tropolone, we have estimated the limit of detection at 3,200 cells, with a radioactive burden of 0.14 Bq per cell (20). Additionally, our group has also shown that application of corrections for Compton scatter, radionuclide crosstalk, and attenuation in SPECT image processing can improve multiisotope detection (11). Therefore, we have shown that multiisotope SPECT can be very sensitive and quantitative.…”

Section: Discussionmentioning

confidence: 96%

“…Recently, our group has developed a method to use multiisotope SPECT for detection of gene expression, cell location, and perfusion to assess the effects of stem cell therapy in a large animal model of myocardial infarct (11). In dogs harboring bone marrow-derived mesenchymal cells expressing HSV1-TK, they were able to simultaneously detect gene expression with 131 I-FIAU, verify the location of the stem cell transplants with 111 In, and assess the effects of stem cell transplantation on myocardial perfusion with 99m Tc-sestamibi (11).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT

Tai¹,

Nguyen²,

Wells³

et al. 2007

J Nucl Med

Self Cite

View full text Add to dashboard Cite

We are combining nuclear medicine with molecular biology to establish a sensitive, quantitative, and tomographic method with which to detect gene expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to image multiple molecular events simultaneously, and coregistration of SPECT and CT images enables visualization of reporter gene expression in the correct anatomic context. We have engineered pancreatic islet cell lines for imaging with SPECT/CT after transplantation under the kidney capsule. Methods: INS-1 832/13 and aTC1-6 cells were stably transfected with a herpes simplex virus type 12thymidine kinase2green fluoresecent protein (HSV1-thymidine kinase-GFP) fusion construct (tkgfp). After clonal selection, radiolabel uptake was determined by incubation with 5-131 I-iodo-1-(2-deoxy-2-fluoro-b-D-arabinofuranosyl)uracil ( 131 I-FIAU) (aTC1-6 cells) or 123 I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after aTC1-6/tkgfp cells had been labeled with either 131 I-FIAU or 111 In-tropolone and transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT images were coregistered to CT. In a second study using simultaneous acquisition dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with 111 In-tropolone before transplantation. Mice were then systemically administered 123 I-FIAU and data for both 131 I and 111 In were acquired simultaneously. Results: aTC1-6/tkgfp cells showed a 15-fold greater uptake of 131 I-FIAU, and INS-1/tkgfp cells showed a 12-fold greater uptake of 123 I-FIAU, compared with that of wild-type cells. After transplantation under the kidney capsule, both reporter gene expression and location of cells could be visualized in vivo with dual-isotope SPECT. Immunohistochemistry confirmed the presence of glucagon-and insulin-positive cells at the site of transplantation. Conclusion: Dual-isotope SPECT is a promising method to detect gene expression in and location of transplanted pancreatic cells in vivo.

show abstract

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT

Tai¹,

Nguyen²,

Wells³

et al. 2007

J Nucl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, radiolabeled oligonucleotide can bind an mRNA transcript and radiolabeled antibodies/antibody-like structures can target cell-surface proteins [76]. Radioactive atoms, including 99mTc and 111In have been commonly used for labeling pre-transplant cells such as MSCs and proven effective without affecting the viability and differentiation capacity of the MSCs [75,79,80]. In addition, dual labeling has been performed.…”

Section: Nuclear Imagingmentioning

confidence: 99%

“…PET detects two anti-parallel 511-keV gamma rays and it has a higher sensitivity than SPECT, and thus, more accurate in quantification analysis. Methods for stem cell labeling involves direct loading with a radiometal [73][74][75] and indirect labeling through enzymatic conversion and retention of a radioactive materials or receptor mediated binding [74,76,77].…”

Section: Nuclear Imagingmentioning

confidence: 99%

Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers

et al. 2009

View full text Add to dashboard Cite

Stem cell-based therapy for patients with postinfarct heart failure is a relatively new and revolutionary concept in cardiology. Despite the encouraging results from pre-clinical studies, outcomes from most clinical trials remain moderately positive while the clinical benefits are largely attributed to transplanted cell-associated paracrine effects in stimulating angiogenesis and protecting endogenous cardiomyocytes. This scenario indicates that there may be a considerably protracted iterative process of conceptual and procedural refinement before true clinical benefits can be fully materialized. At present, many pressing questions regarding cell therapy remain unanswered. In addition to the primary interest in determining the ideal type of stem cells with best cardiogenic potential in vitro and in vivo, there are growing concerns on the impact of the host cardiac milieu on the transplanted cells, including their survival, migration, engraftment, and transdifferentiation as well as contribution to left ventricular function. Effective cell delivery and tracking methods are central to the unraveling of these questions. To date, celldelivery modalities are yet to be optimized and strategies for safe and effective assessment of cells transplanted in the recipients are to be established. In this review, we discuss cell delivery and tracking modalities that are adopted in the current pre-clinical and clinical studies. We further discussed emerging technologies that are poised to impact the success of cell therapy.

show abstract

“…This includes the lack of immunogenicity of the human NIS transgene and the fact that SPECT scanning of radiotracers such as 99m Tc and 123 I is widely available at relatively low cost and is approved by responsible regulatory authorities such as the Food and Drug Administration. Moreover, recent progress in quantification of tracer signals with the use of clinical SPECT systems 21 emphasizes the potential of this approach for tracking cellular transplants in large animals and patients. To date, however, the strategy was evaluated only in a small-animal model focused on detection of acute cell retention after administration of cardiac derived stem cells.…”

Section: Editorial See P 388 Clinical Perspective On P 439mentioning

confidence: 99%

Transplantation and Tracking of Human-Induced Pluripotent Stem Cells in a Pig Model of Myocardial Infarction

et al. 2012

View full text Add to dashboard Cite

Background-Evaluation of novel cellular therapies in large-animal models and patients is currently hampered by the lack of imaging approaches that allow for long-term monitoring of viable transplanted cells. In this study, sodium iodide symporter (NIS) transgene imaging was evaluated as an approach to follow in vivo survival, engraftment, and distribution of human-induced pluripotent stem cell (hiPSC) derivatives in a pig model of myocardial infarction. Methods and Results-Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NIS pos -hiPSCs) were established. Iodide uptake, efflux, and viability of NIS pos -hiPSCs were assessed in vitro. Ten (Ϯ2) days after induction of myocardial infarction by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NIS pos -hiPSCs guided by 3-dimensional NOGA mapping was performed. Dual-isotope single photon emission computed tomographic/computed tomographic imaging was applied with the use of 123 I to follow donor cell survival and distribution and with the use of 99m TC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NIS pos -hiPSCs was increased 100-fold above that of nontransgenic controls. In vivo, viable NIS pos -hiPSCs could be visualized for up to 15 weeks. Immunohistochemistry demonstrated that hiPSC-derived endothelial cells contributed to vascularization. Up to 12 to 15 weeks after transplantation, no teratomas were detected. S tem cell-based therapies are being actively explored as a potentially innovative therapeutic strategy for various genetic and acquired diseases. Recently, the possibility of reprogramming human somatic cells into human-induced pluripotent stem cells (hiPSCs) that are able to differentiate into all cell lineages present in the heart 1-4 has opened novel opportunities for myocardial repair. With respect to the potential therapeutic application of pluripotent stem cell derivatives, major progress Conclusions-This Editorial see p 388 Clinical Perspective on p 439However, there are still major hurdles and risks to overcome with regard to PSC-based heart repair. These include safety risks, especially the potential of teratoma and tumor formation, 2 low cell retention and engraftment rates, 8 -11 and the general question of whether engraftment of hiPSCs after simple intramyocardial cell injection leads to formation of functional tissue, such as de novo vasculature or myocardium, and results in significant clinical benefits. 12 Although some of these issues can be addressed in vitro or in appropriate small-animal models, others will require exploration in large-animal models, which are more similar to humans. 13 Transplanted human cardiomyocytes, for example, are unlikely to fully functionally integrate with rodent myocardium because of highly dissimilar beating rates. 11 Therefore, meaningful assessment of human cells for heart repair must be demonstrated in large-animal models such as dogs, pigs, or monkeys. 13 Clearly, advanced imaging technologies allowing for l...

show abstract

A method for quantitative cell tracking using SPECT for the evaluation of myocardial stem cell therapy

Abstract: In dual-isotope SPECT, corrections for physical effects were required to detect transgene expression in cells transplanted into an infarction when localization information was available.

Cited by 21 publications

References 28 publications

Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT

Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT

Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers

Transplantation and Tracking of Human-Induced Pluripotent Stem Cells in a Pig Model of Myocardial Infarction

Contact Info

Product

Resources

About