scholarly journals In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5069
Author(s):  
Massis Krekorian ◽  
Kimberley R. G. Cortenbach ◽  
Milou Boswinkel ◽  
Annemarie Kip ◽  
Gerben M. Franssen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Tracking ◽  
Immune Cell ◽  
Specific Activity ◽  
Ex Vivo ◽  
Cell Labeling ◽  
Aureus Infection ◽  
Cell Based Therapy ◽  
Number Of Cells

The exponential growth of research on cell-based therapy is in major need of reliable and sensitive tracking of a small number of therapeutic cells to improve our understanding of the in vivo cell-targeting properties. 111In-labeled poly(lactic-co-glycolic acid) with a primary amine endcap nanoparticles ([111In]In-PLGA-NH2 NPs) were previously used for cell labeling and in vivo tracking, using SPECT/CT imaging. However, to detect a low number of cells, a higher sensitivity of PET is preferred. Therefore, we developed 89Zr-labeled NPs for ex vivo cell labeling and in vivo cell tracking, using PET/MRI. We intrinsically and efficiently labeled PLGA-NH2 NPs with [89Zr]ZrCl4. In vitro, [89Zr]Zr-PLGA-NH2 NPs retained the radionuclide over a period of 2 weeks in PBS and human serum. THP-1 (human monocyte cell line) cells could be labeled with the NPs and retained the radionuclide over a period of 2 days, with no negative effect on cell viability (specific activity 279 ± 10 kBq/106 cells). PET/MRI imaging could detect low numbers of [89Zr]Zr-THP-1 cells (10,000 and 100,000 cells) injected subcutaneously in Matrigel. Last, in vivo tracking of the [89Zr]Zr-THP-1 cells upon intravenous injection showed specific accumulation in local intramuscular Staphylococcus aureus infection and infiltration into MDA-MB-231 tumors. In conclusion, we showed that [89Zr]Zr-PLGA-NH2 NPs can be used for immune-cell labeling and subsequent in vivo tracking of a small number of cells in different disease models.

Non-radioactive imaging strategies for in vivo immune cell tracking

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Łukasz Kiraga ◽  
Paulina Kucharzewska ◽  
Damian Strzemecki ◽  
Tomasz P. Rygiel ◽  
Magdalena Król
Keyword(s):  
Diagnostic Imaging ◽  
Contrast Agents ◽  
Cell Tracking ◽  
Immune Cell ◽  
Imaging Techniques ◽  
Diagnostic Technique ◽  
Cell Labeling ◽  
X Ray Imaging ◽  
Disease Study

Abstract In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.

Abstract 1767: Feasibility of In Vivo Cardiac Stem Cell Tracking, by SPECT and PET Imaging, Using the Sodium-iodide Symporter as Reporter Gene

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
John Terrovitis ◽  
Keng Fai Kwok ◽  
Riikka Läutamaki ◽  
James M Engles ◽  
Andreas S Barth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Reporter Gene ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Small Animal ◽  
Cell Labeling ◽  
Sodium Iodide Symporter ◽  
Cell Injection

Background. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo . Aim. To develop a reporter gene that permits in vivo stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of 99m Tc or 124 I, thus permitting cell tracking by SPECT or PET imaging, respectively. Methods. The human NIS gene ( h NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by in vitro 99m Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using 99m Tc for cell detection and 201 Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using 124 I for cell tracking and 13 NH 3 for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution ex vivo SPECT scans of explanted hearts (n=3) were obtained to confirm that in vivo signal was derived from the cell injection site. The presence of h NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR. Results. NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro 99m Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of 99m Tc or 124 I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that in vivo 99m Tc signals were localized to the injection sites. PCR confirmed the presence of h NIS mRNA in injected hearts. Conclusion. NIS expression allows non invasive in vivo stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.

scholarly journals Nuclear imaging for immune cell tracking in vivo – Comparison of various cell labeling methods and their application

2021 ◽  
Vol 445 ◽  
pp. 214008
Author(s):  
Łukasz Kiraga ◽  
Paulina Kucharzewska ◽  
Stephen Paisey ◽  
Łukasz Cheda ◽  
Anita Domańska ◽  
...  
Keyword(s):  
Cell Tracking ◽  
Immune Cell ◽  
Nuclear Imaging ◽  
Cell Labeling

scholarly journals Advances in Molecular Imaging Strategies forIn VivoTracking of Immune Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ho Won Lee ◽  
Prakash Gangadaran ◽  
Senthilkumar Kalimuthu ◽  
Byeong-Cheol Ahn
Keyword(s):  
Computerized Tomography ◽  
Immune Cells ◽  
Cell Tracking ◽  
Immune Cell ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Nuclear Imaging ◽  
Cell Based Therapy

Tracking of immune cellsin vivois a crucial tool for development and optimization of cell-based therapy. Techniques for tracking immune cells have been applied widely for understanding the intrinsic behavior of immune cells and include non-radiation-based techniques such as optical imaging and magnetic resonance imaging (MRI), radiation-based techniques such as computerized tomography (CT), and nuclear imaging including single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Each modality has its own strengths and limitations. To overcome the limitations of each modality, multimodal imaging techniques involving two or more imaging modalities are actively applied. Multimodal techniques allow integration of the strengths of individual modalities. In this review, we discuss the strengths and limitations of currently available preclinicalin vivoimmune cell tracking techniques and summarize the value of immune cell tracking in the development and optimization of immune cell therapy for various diseases.

scholarly journals Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

2021 ◽  
Author(s):  
Massis Krekorian ◽  
Gerwin G. W. Sandker ◽  
Kimberley R. G. Cortenbach ◽  
Oya Tagit ◽  
N. Koen van Riessen ◽  
...  
Keyword(s):  
Glycolic Acid ◽  
Ex Vivo ◽  
Cell Labeling ◽  
Autologous Cell

Prevention of Panton-Valentine Toxin-Mediated Leucocyte Destruction Depending on the Ultra-Diluted Staphylococcinum Potency Gradient

2020 ◽  
Vol 33 (02) ◽  
pp. 099-103
Author(s):  
Pritam Goswami ◽  
Sayak Ghosh ◽  
Sk Swaif Ali ◽  
Anamika Basu ◽  
Joydeep Khanra ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Ecological Niche ◽  
Staphylococcal Infection ◽  
Buffy Coat ◽  
Preventive Action ◽  
Phagocytic Cells ◽  
Mortality And Morbidity ◽  
Aureus Infection ◽  
The Mean

Abstract Background Panton-Valentine toxin (PVT) is an important pathological marker of staphylococcal infection mediated by functional as well as morphological damage of the phagocytic cells. Human body being an ecological niche for the bacteria shows higher affinity toward staphylococcal infection. A steady escalation in mortality and morbidity associated with antibiotic resistance in gram-positive infections is an emerging threat all over the globe; thus, it is important to find out an alternative strategy that can diminish the virulence and pathogenicity of the bacteria. Staphylococcin is a colicin-type chemical secreted by Staphylococcus aureus helps to prevent growth of organisms other than its progenitor. In this study, we evaluated the efficacy of homoeopathic medicine Staphylococcinum against staphylococcal PVT at different potencies (6CH, 12CH, 30CH and 200CH). Materials and Methods Different potencies of Staphylococcinum were administered in a leucocyte buffy coat preparation infected with staphylococcal suspension (0.5 McFarland's standard) along with control with alcohol. They were kept in incubator for 2 hours and then centrifuged at 1200 rpm for 5 minutes. Smears prepared on slides with centrifuged deposits stained by Preston and Morrell's modified Gram's method of staining and evaluated under the microscope. Results It was observed that there was extensive destruction of leukocytes in control and 6CH potency, while the degree of destruction decreased markedly from 12CH to 200CH. At 200CH potency, leukocytes were almost normal, which clearly indicate the preventive action of Staphylococcinum against PVT. The mean percentages of intact leucocytes were 0.73, 0.93, 10.00, 27.67 and 65.00 in control, 6CH, 12CH, 30CH and 200CH potencies, respectively. Conclusion The finding may help in the use of this medicine in moribund patients in cases of disseminated S. aureus infection as there is no known side effect of the medicine. However, in vivo study is necessary before such use in those cases.

Inorganic Nanoparticles and Nanomaterials Based on Titanium (Ti): Applications in Medicine

2013 ◽  
Vol 754 ◽  
pp. 21-87 ◽  
Author(s):  
Zeid A. Al Othman ◽  
Mohammad Mezbaul Alam ◽  
Mu. Naushad ◽  
Inamuddin ◽  
Mohd Farhan Khan
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Cell Tracking ◽  
Conventional Medicine ◽  
Inorganic Nanoparticles ◽  
Cell Labeling ◽  
Body Parts ◽  
Drug And Gene Delivery

Nanomedicine is a relatively new field of science and technology. By interacting with biomolecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Current and potential applications of nanotechnology in medicine range from research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering procedures. Its advantage over conventional medicine lies on its size. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. This allows drugs of nanosize be used in lower concentration and has an earlier onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a specific location. Inorganic nanomedicine is likely to remain one of the most prolific fields of nanomedicine, which refers to the use of inorganic or hybrid (inorganic-inorganic or inorganic-organic) nanomaterials (INMs) and nanoparticles (INPs) to achieve innovative medical advances for body parts implantation, drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Among the most promising INMs being developed are metal, silica, dendrimers, organic-inorganic hybrids, ceramics (e.g. ZrO2, TiO2, Al2O3, etc.) and bioinorganic hybrids. Metal NP contrast agents enhance magnetic resonance imaging and ultrasound results in biomedical applications of in vivo imaging. Hollow and porous INMs have been exploited for drug and gene delivery, diagnostic imaging, and photothermal therapy. Biomolecular inorganic nanohybrids and nanostructured biomaterials have been exploited for targeted imaging and therapy, drug and gene delivery, and regenerative medicine. Potential uses for fluorescent quantum dots (QDs) include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastasis cell tracking. This article outlines present developments and future prospects for the use of Ti-based NPs and NMs in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use in diagnosis and therapy in diverse fields of medical sciences, such as oncology, infection control, orthopedics, dentistry, dermatology, genetics, cardiology, ophthalmology, etc. Toxicological considerations of these INPs and INMs are also discussed.

Abstract 2876: Early Retention and Subsequent Engraftment of Transplanted Progenitor Cells is Improved by Delivery within Collagen Matrix

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yan Zhang ◽  
Marc Lamoureux ◽  
Stephanie Thorn ◽  
Vincent Chan ◽  
Joel Price ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Progenitor Cells ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Collagen Matrix ◽  
Cell Labeling ◽  
Type I ◽  
The Matrix ◽  
Early Retention

Background: To investigate the mechanisms involved in the potentiation of cell therapy by delivery matrices, we evaluated the retention and engraftment of transplanted human circulating progenitor cells (CPCs) injected in a collagen matrix by using in vivo positron emission tomography (PET) imaging, ex vivo biodistribution, and immunohistochemistry. Methods: CPCs were labeled with 18 F-FDG and injected with or without a collagen type I-based matrix in the ischemic hindlimb muscle (IM) of rats (2x10 6 cells; n=15/group). Localization of cells was acquired by PET imaging (15 min) at 150 min post-injection. In addition, radionuclide biodistribution, immunofluorescence, and immunohistochemical examination of transplanted CPCs were performed at up to 14 days. Results: Cell labeling efficiency was CPC-concentration dependent (r=0.61, p <0.001), but not 18 F-FDG-dose dependent. Labeled CPCs exhibited excellent short-term stability and viability. Persistence of 18 F-FDG radioactivity in cells was markedly greater than non-specific retention in the matrix. Wholebody (WB) PET images revealed better CPC retention in the IM and less non-specific leakage to other tissues when CPCs were delivered within the matrix (IM/WB retention ratio of 43.9±8.2%), compared to cells injected alone (22.3±10.4%; p =0.040) and to 18 F-FDG injected with or without the matrix (9.7±5.5% and 11.0±5.5%, respectively; p <0.005). Radioactivity biodistribution confirmed that accumulation was increased (by 92.5%; p =0.024) in the IM and reduced (by 1.1 to 23.8%; p <0.05) in non-specific tissues when cells were injected within the matrix, compared to cells injected alone. Anti-human mitochondria staining showed increased cell retention in the IM with use of matrices (3.0±2.1%) versus cells only (1.9±0.8%; p =0.048). At 14 days the number of CD31 + transplanted human cells was greater (1.6±0.1%) when injected within the matrix than injected alone (0.7±0.1%; p =0.004). Conclusions: Collagen-based delivery matrices improve the early retention of transplanted CPCs, which in turn favors subsequent cell engraftment in the ischemic tissue. This mechanism conferred by the matrix has potential implications for the optimization of cell therapy at the early stages after cell delivery.

scholarly journals Rabbit model of Staphylococcus aureus implant-associated spinal infection

2020 ◽  
Vol 13 (7) ◽  
pp. dmm045385
Author(s):  
Oren Gordon ◽  
Robert J. Miller ◽  
John M. Thompson ◽  
Alvaro A. Ordonez ◽  
Mariah H. Klunk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Remodeling ◽  
Ex Vivo ◽  
Rabbit Model ◽  
Pedicle Screws ◽  
Lumbar Vertebra ◽  
Wound Dehiscence ◽  
Spinal Infection ◽  
Positron Emission

ABSTRACTPost-surgical implant-associated spinal infection is a devastating complication commonly caused by Staphylococcus aureus. Biofilm formation is thought to reduce penetration of antibiotics and immune cells, contributing to chronic and difficult-to-treat infections. A rabbit model of a posterior-approach spinal surgery was created, in which bilateral titanium pedicle screws were interconnected by a plate at the level of lumbar vertebra L6 and inoculated with a methicillin-resistant S.aureus (MRSA) bioluminescent strain. In vivo whole-animal bioluminescence imaging (BLI) and ex vivo bacterial cultures demonstrated a peak in bacterial burden by day 14, when wound dehiscence occurred. Structures suggestive of biofilm, visualized by scanning electron microscopy, were evident up to 56 days following infection. Infection-induced inflammation and bone remodeling were also monitored using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and computed tomography (CT). PET imaging signals were noted in the soft tissue and bone surrounding the implanted materials. CT imaging demonstrated marked bone remodeling and a decrease in dense bone at the infection sites. This rabbit model of implant-associated spinal infection provides a valuable preclinical in vivo approach to investigate the pathogenesis of implant-associated spinal infections and to evaluate novel therapeutics.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

2019 ◽  
Vol 15 (11) ◽  
pp. 2179-2192
Author(s):  
Yuanyuan Xie ◽  
Wei Liu ◽  
Bing Zhang ◽  
Bin Wang ◽  
Liudi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

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