Biology subjects

Foster, P. J.

Publications and source records attributed to Foster, P. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparative Evaluation of Commercial Iron Oxide Particles for Magnetic Particle Imaging Using Relaxometry and Image-Based Metrics

In magnetic particle imaging (MPI), signal is generated from the non-linear magnetic response of superparamagnetic iron oxide (SPIO) nanoparticles. The optimization of SPIOs for MPI is an active area of investigation. Tracer performance can be evaluated by magnetic particle relaxometry (MPR) and image-based metrics. This study characterized and compared the performance of ten commercially available tracers, spanning a broad range of magnetic core sizes, hydrodynamic diameters and surface coatings, using the peak signal intensity measured from MPR, and the total signal and maximum signal intensity measured from 2D MPI images. Synomag-D tracers exhibited the highest MPR peak signal intensities and highest maximum signal per {micro}g iron. ProMag, a micron-sized iron oxide particle (MPIO), yielded a low MPR peak signal intensity but had the highest total MPI signal per {micro}g of iron. A strong correlation was observed between MPR peak signal intensity and MPI maximum signal intensity (R2=0.94). In contrast, there was a weak correlation between MPR peak signal intensity and MPI total signal intensity (R2=0.38), though this correlation improved when MPIOs were excluded from the analysis (R2=0.91). While MPR generally predicts the tracer performance, it does not completely replicate the complex imaging conditions. As such, comprehensive tracer evaluation requires combining both MPR and image-based metrics.

biophysics↗

bioRxiv2025

Magnetic Particle Imaging Lymphography (MPIL): A novel technique for lymph node mapping

During metastasis, tumour cells drain to nearby lymph nodes, the first of which are named the sentinel lymph node(s) (SLN). SLN biopsy (SLNB) determines if metastasis has occurred. Traditionally, SLNB involves injecting a Technetium-labeled tracer peritumourally, pre-operative imaging with SPECT to locate the SLN, and surgery guided by a gamma probe to remove them. Limitations include short tracer half-life which can make scheduling the SLNB difficult, and radiation dose to patients and healthcare workers. Alternatively, magnetic localization, with superparamagnetic iron oxide nanoparticles (SPIONs) as the tracer and a magnetometer to detect SPIONs in the SLN during surgery can be used, however, this lacks pre-operative imaging. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIONs, holding potential for pre-operative imaging in magnetic SLNB. SPIONs for SLNB should have rapid drainage, high SLN accumulation, and high specificity to the SLN. For MPI Lymphography (MPIL), high particle sensitivity is also important. This study assesses the in vivo pharmacokinetics for SLN mapping with MPIL in a murine model, using five commercially available SPIONs of varying iron core sizes and surface coatings. We show that some SPIONs provide higher MPI signal at the SLN and show the potential to detect higher echelon nodes (HENs). PEGylation of SPIONs and mannose targeted SPIONs increase clearance from the injection site and the mannose targeted SPION reduces flow to HENs.

biophysics↗

bioRxiv2024

Advances in magnetic particle imaging: evaluating magnetic microspheres and optimized acquisition parameters for high sensitivity cell tracking

MotivationThe sensitivity and resolution of magnetic particle imaging (MPI) depend on the choice of tracer and specific imaging parameters. For cell tracking applications with MPI, both the superparamagnetic iron oxide (SPIO) tracer and the cell labeling efficiency have a significant impact on MPI sensitivity and vary for different tracers. ObjectiveThis study compared three commercially available SPIO tracers (VivoTrax, Synomag-D and ProMag) and SPIO-labeled cells using magnetic particle relaxometry (MPR) and imaging. Further, the effect of imaging parameters (gradient field strength and drive field amplitude) on MPI signal strength, resolution, and cell detection limits, was evaluated. ResultsThe peak MPI signal measured by MPR was much higher for Synomag-D compared to VivoTrax and ProMag. However, the signal for intracellular Synomag-D was significantly reduced. In contrast, the signal for ProMag, a micron-sized iron oxide (MPIO) particle, was not significantly different for free and intracellular particles. The cellular iron loading was higher for ProMag compared to Synomag-D. The total MPI signal measured from images of free and intracellular SPIOs was highest for ProMag. Varying imaging parameters confirmed that a lower gradient field strength and higher drive field amplitude improved tracer and cellular sensitivity. ConclusionThese results show that the evaluation of tracers by MPR is not sufficient to predict the performance of all SPIO tracers; in particular, not for larger, polymer-encapsulated iron particles such as ProMag, or for SPIO tracers internalized in cells. Improvements in MPI sensitivity through lower gradient field strength and higher drive field amplitudes are associated with a trade-off in image resolution.

biophysics↗

bioRxiv2023

Multichannel joint image reconstruction allows for artifact-free focused small field of view magnetic particle imaging

Tumour Associated Macrophages (TAMs) play a crucial role in breast cancer progression and have the potential to be used as a biomarker for patient prognosis. Magnetic particle imaging (MPI) is an emerging modality which can detect cells labelled with superparamagnetic iron oxide (SPIO) nanoparticles and can be used for non-invasive TAM assessment. However, MPI TAM detection is limited by its effective dynamic range. This limitation occurs when SPIO nanoparticles injected intravenously accumulate in the liver resulting in a large MPI signal which shadows regions of interest with lower signals (i.e the tumour) preventing their isolation and quantification. In this study we test an advanced reconstruction algorithm which allows us to prescribe a small focused field of view (FOV) on lower signals of interest. We then demonstrate the success of this method with an in vivo tumour model and show enhanced image quality and successful quantification of TAMs in mouse mammary tumours with different metastatic potentials (4T1 and E0771). Utilizing in vivo MPI, we did not see significant differences in the MPI signal for 4T1 tumours compared to E0771. These findings highlight the potential of MPI for in vivo TAM quantification offering a promising avenue for broader applications in cancer research and potentially overcoming constraints of MPI in other in vivo imaging contexts.

biophysics↗

bioRxiv2023

Inter-user comparison for quantification of superparamagnetic iron oxides with magnetic particle imaging across two institutions highlights a need for standardized approaches

PurposeMagnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. ProceduresSix users (3 from each institute) imaged a known amount of Vivotrax+ (10 g Fe), diluted in a small (10 L) or large (500 L) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users x triplicate samples x 2 sample volumes x 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax+ quantification, and ROI selection was compared across users, within and across institutions. ResultsMPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax+. Overall quantification yielded measurements that were within {+/-} 20% from ground truth, however SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. ConclusionsThis study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental set up, image acquisition parameters, and ROI selection analysis.

biophysics↗

bioRxiv2023

In vivo tracking of adenoviral-transduced iron oxide-labeled bone marrow-derived dendritic cells using magnetic particle imaging

BackgroundDespite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo post-injection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Preliminary studies have identified magnetic particle imaging (MPI) as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide-(SPIO)-labeled DC. Herein, we describe a lymph node- (LN)-focused MPI scan to quantify DC in vivo migration accurately and consistently. MethodsBoth adenovirus (Ad)-transduced SPIO+ (Ad SPIO+) and SPIO+ C57BL/6 bone marrow-derived DC were generated and assessed for viability and phenotype using flow cytometry. Ad SPIO+ and SPIO+ DC were fluorescently-labeled and injected into C57BL/6 mouse hind footpads (n=6). Two days later, in vivo DC migration was quantified using whole animal, popliteal LN- (pLN)-focused, and ex vivo pLN MPI scans. ResultsNo significant differences in viability, phenotype and in vivo pLN migration were noted for Ad SPIO+ and SPIO+ DC. Day 2 pLN-focused MPI successfully quantified DC migration in all instances while whole animal MPI only quantified pLN migration in 75% of cases. Ex vivo MPI and fluorescence microscopy confirmed MPI signal was pLN-localized and due to originally-injected Ad SPIO+ and SPIO+ DC. ConclusionsWe overcame a reported limitation of MPI by using a pLN-focused MPI scan to quantify pLN-migrated Ad SPIO+ and SPIO+ DC in 100% of cases. With this improved method, we detected as few as 1000 DC (4.4 ng Fe) in vivo. MPI is a suitable pre-clinical imaging modality to assess DC-based cancer immunotherapeutic efficacy.

immunology↗

bioRxiv2023

Microscopic interactions control a structural transition in active mixtures of microtubules and molecular motors

Microtubules and molecular motors are essential components of the cellular cytoskeleton, driving fundamental processes in vivo, including chromosome segregation and cargo transport. When reconstituted in vitro, these cytoskeletal proteins serve as energy-consuming building blocks to study the self-organization of active matter. Cytoskeletal active gels display rich emergent dynamics, including extensile flows, locally contractile asters, and bulk contraction. However, how the protein-protein interaction kinetics set their contractile or extensile nature is unclear. Here, we explore the origin of the transition from extensile bundles to contractile asters in a minimal reconstituted system composed of stabilized microtubules, depletant, ATP, and clusters of kinesin-1 motors. We show that the microtubule binding and unbinding kinetics of highly processive motor clusters set their ability to end-accumulate, which can drive polarity sorting of the microtubules and aster formation. We further demonstrate that the microscopic time scale of end-accumulation sets the emergent time scale of aster formation. Finally, we show that biochemical regulation is insufficient to explain fully the transition as generic aligning interactions through depletion, crosslinking, or excluded volume interactions can drive bundle formation, despite the presence of end-accumulating motors. The extensile-to-contractile transition is well captured by a simple self-assembly model where nematic and polar aligning interactions compete to form either bundles or asters. Starting from a five-dimensional organization phase space, we identify a single control parameter given by the ratio of the different component concentrations that dictates the material-scale organization. Overall, this work shows that the interplay of biochemical and mechanical tuning at the microscopic level controls the robust self-organization of active cytoskeletal materials. Significance statementSelf-organization in living cells is often driven by energy-consuming motor proteins that push and pull on a network of cytoskeletal filaments. However, it is unclear how to connect the emergent structure and dynamics of reconstituted cytoskeletal materials to the kinetics and mechanics of their microscopic building blocks. Here, we systematically correlate bulk structure with asymmetry of the motor distribution along single filaments to explain the transition from extensile bundles to contractile asters in active networks of stabilized microtubules crosslinked by motor proteins. We combine experiments and scaling arguments to identify a single number that predicts how the system will self-organize. This work shows that biochemical and mechanical interactions compete to set the emergent structure of active biomimetic gels.

biophysics↗

bioRxiv2022

Active mechanics of sea star oocytes

Cell shape changes, driven by the contractile actomyosin cortex, are essential for multicellular organisms. Yet, how contractility and cell shape changes emerge from molecular scale interactions between proteins in the actomyosin cortex remains unclear. Oocytes of the bat star Patiria miniata exhibit a traveling wave of cellular deformation during meiosis, known as a surface contraction wave (SCW). Here, we exploit this highly stereotypical deformation to study how cortical properties are set by microscale processes. By pharmacologically modulating the levels of polymerized actin, we show that the wildtype composition maximizes the cellular deformation rate. To understand these results, we developed an active fluid model for shape changes that demonstrates that deformation rates are set by the ratio between cortical viscosity and active contractile stresses and provides a framework for deriving these two key material properties from coarse-grained molecular-scale interactions. In this model, the ratio of active stress to viscosity peaks at intermediate admixtures of passive crosslinkers. This explains the observations of the drug treatment experiments and makes additional predictions, namely that overexpression of either myosin or passive crosslinkers would decrease deformation rates, which we verified experimentally. Together, this shows that the interplay between cortical active stress and viscosity relies on balancing the ratio of myosin to passive crosslinkers on each filament, which can be modulated by actin density. Our results argue that changing the relative molecular compositions of cortical crosslinks and motors provides a mechanism that biological systems could exploit for robust and predictable control over both viscosity and active stresses.

biophysics↗

bioRxiv2022

MPI region of interest (ROI) analysis and quantification of iron in different volumes

MPI directly detects superparamagnetic iron oxides (SPIONs), which should enable precise, accurate, and linear quantification. However, selecting a region of interest (ROI) has strong effects on MPI quantification results. Ideally, ROI selection should be simple, user-independent, and widely applicable. In this work, we describe and compare four MPI ROI selection methods and assess their performance in vitro and in vivo. To explore the effect of ROI selection, ten ferucarbotran phantoms were imaged, each contained the same amount of iron but varied in volume. Three users tested the accuracy of the ROI methods for quantification of these samples. Lastly, the four ROI methods were applied to quantify ferucarbotran in vivo after intravenous, intramuscular, and subcutaneous injections in mice. We demonstrate that each ROI method has strengths. We conclude there is an important trade-off between ROI size and the accuracy of iron quantification, therefore the choice of ROI selection method for each study must be carefully informed.

biophysics↗

bioRxiv2021

Tracking the fates of iron-labeled tumor cells in vivo using Magnetic Particle Imaging

The use of imaging to detect and monitor the movement and accumulation of cells in living subjects can provide significant insights that can improve our understanding of metastasis and guide therapeutic development. For cell tracking using Magnetic Resonance Imaging (MRI), cells are labeled with iron oxides and the effects of the iron on water provides contrast. However, due to low specificity and difficulties in quantification with MRI, other modalities and approaches need to be developed. Magnetic Particle Imaging (MPI) is an emerging imaging technique which directly detects magnetic iron, allowing for a specific, quantitative and sensitive readout. Here, we use MPI to image iron-labeled tumor cells longitudinally, from implantation and growth at a primary site to movement to distant anatomic sites. In vivo bioluminescent imaging (BLI) was used to localize tumor metastases and computed tomography (CT) allowed for correlation of these signals to anatomic locations. These three imaging modalities provide information on immune escape and metastasis of iron-labeled, and unlabeled, tumor cells, and the accumulation of cell-free iron contrast over time. We identified iron signals by MPI and tumor cells via BLI, and correlated these positive contrast images with CT scans to reveal the anatomic sites with cancer cells; histologic analysis confirmed the presence of iron-labeled tumor cells in the tissues, suggesting that the metastatic cells retained enough iron for MPI detection. The use of multi-modality cell tracking reveals the movement, accumulation and fates of labeled cells that will be helpful understanding cancer progression and guiding the development of targeted therapies.

biophysics↗

bioRxiv2021

Magnetic Particle Imaging is a sensitive in vivo imaging modality for the quantification of dendritic cell migration

Immunotherapies, such as dendritic cell- (DC-)based therapies, are useful for treating cancer as an alternative to or in combination with traditional therapies. Cells must migrate to lymphoid organs to be effective and the magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With less than 10% of cells expected to reach their destination, there is a need for an imaging modality capable of sensitively and quantitatively detecting cells. MRI has been used to track DC using iron and 19F methods, with limitations. Quantification of iron-induced signal loss is indirect and challenging; 19F signal is directly quantifiable but lacks sensitivity. Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide nanoparticles (SPIO) and enables quantitation of low numbers of SPIO-labeled cells. Here we describe the first study using MPI to track and quantify the migration of DC, injected into the footpads of C57BL/6 mice, to the popliteal lymph nodes (pLNs). As DC migrate from the site of injection to the lymph nodes, we measured a decrease in signal in the footpads and an increase in signal at the pLNs. The presence of SPIO-labeled DC in nodes was validated by ex vivo MPI and histology. By measuring the iron mass per cell in samples of labeled cells, we were able to provide an estimate of cell number for each source of signal and we report a sensitivity of approximately 4000 cells in vivo and 2000 cells ex vivo. For some mice, MPI was compared to cellular MRI. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for many pre-clinical studies using a highly concentrated tracer bolus that over shadows nearby lower signals. This study demonstrates the clear advantage of MPI to detect and quantify cells in vivo, bridging the gap left by cellular MRI, and all other in vivo imaging modalities, and opening the door for quantitative imaging of cellular immunotherapies.

biophysics↗

bioRxiv2021

The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking

PurposeMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells. MethodsCells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. ResultsUsing the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 x 1016 19F atoms) were detected with 19F MRI, with SNR > 5. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. ConclusionMPI has the potential to be more sensitive than 19F MRI for cell tracking. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

biophysics↗

bioRxiv2021

A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation

There is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumour behavior, and metastatic properties observed in the original tumour. These models are more predictive of clinical outcomes and are superior to cell lines for preclinical drug evaluation and therapeutic strategies. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metastases and validate this method with imaging during tumour development. Luciferase expressing human breast cancer PDX cells (F2-7) were successfully labeled after incubation with micron-sized iron oxide particles (MPIO; 25 g Fe/mL). NOD/SCID/ILIIrg-/- (n=5) mice received injections of 1x106 iron-labeled F2-7 cells into the fourth mammary fat pad (MFP). BLI was performed longitudinally to day 49 and MPI was performed up to day 28. In vivo BLI revealed that signal increased over time with tumour development. MPI revealed decreasing signal in the tumours and increasing signal in the liver region over time. Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumour. To accomplish this, we also demonstrate the first successful labeling of PDX cells with iron oxide particles. Imaging of PDX cells provides a powerful system to better develop personalized therapies targeting breast cancer brain metastasis.

biophysics↗

bioRxiv2020

Development of Magnetic Particle Imaging (MPI) for Cell Tracking and Detection

IntroductionMagnetic particle imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs) within a sample. SPION-based MRI cell tracking has very high sensitivity, but low specificity and quantification of iron labeled cells is difficult. MPI cell tracking could overcome these challenges. MethodsMDM-AB-231BR cells labeled with MPIO, mice were intracardially injected with either 2.5 x 105 or 5.0 x 105 cells. MRI was performed in vivo the same day at 3T using a bSSFP sequence. After mice were imaged ex vivo with MPI. In a second experiment Mice received an intracardiac injection of either 2.5 x 10 5 or 5 x 10 4 MPIO-labeled 231BR cells. In a third experiment, mice were injected with 5 x 10 4 4T1BR cells, labelled with either MPIO or the SPION Vivotrax. MRI and MPI was performed in vivo. ResultsSignal from MPI and signal voids from MRI both showed more iron content in mice receiving an injection of 5.0 x 105 cells than the 2.5 x 105 injection. In the second experiment, Day 0 MRI showed signal voids and MPI signal was detected in all mouse brains. The MPI signal and iron content measured in the brains of mice that were injected with 2.5 x 10 5 cells were approximately four times greater than in brains injected with 5 x 10 4 cells. In the third experiment, in vivo MRI was able to detect signal voids in the brains of mice injected with Vivotrax and MPIO, although voids were fainter in Vivotrax labeled cells. In vivo MPI signal was only detectable in mice injected with MPIO-labeled cells. ConclusionThis is the first example of the use of MPIO for cell tracking with MPI. With an intracardiac cell injection, approximately 15% of the injected cells are expected to arrest in the brain vasculature. For our lowest cell injection of 5.0 x 104 cells this is [~]10000 cells.

biophysics↗

bioRxiv2020

Visualizing tumour self-homing with magnetic particle imaging

Due to their innate tumour homing capabilities, in recent years, CTCs have been engineered to express therapeutic genes for targeted treatment of primary and metastatic lesions. Additionally, previous studies have incorporated optical or PET imaging reporter genes to enable noninvasive monitoring of therapeutic CTCs in preclinical tumour models. Here, we demonstrate for the first time, the ability of magnetic particle imaging (MPI) to sensitively detect systemically administered iron-labeled CTCs and to visualize tumour self-homing in a murine model of human breast cancer.

biophysics↗

bioRxiv2020

Comparing the fate of brain metastatic breast cancer cells in different immune compromised mice with cellular magnetic resonance imaging

Metastasis is the leading cause of mortality in breast cancer patients, with brain metastases becoming increasingly prevalent. Studying this disease is challenging due to the limited experimental models and methods available. Here, we used iron-based cellular MRI to track the fate of a mammary carcinoma cell line (MDA-MB-231-BR) in vivo to characterize the growth of brain metastases in the nude and severely immune-compromised NOD/SCID/ILIIrg-/- (NSG) mouse. Nude and NSG mice received injections of iron-labeled MDA-MB-231-BR cells. Images were acquired with a 3T MR system and assessed for signal voids and metastases. The percentage of signal voids and the number and volume of metastases were quantified. Ex vivo imaging of the liver, histology, and immunofluorescence labeling was performed. On day 0, iron-labeled cells were visualized as signal voids throughout the brain. The percentage of voids decreased significantly between day 0 and endpoint. At endpoint, there was no difference in the number of brain metastases or tumour burden in NSG mice compared to nudes. Tumour volumes in nude mice were significantly larger than in NSG mice. Body images indicated that the NSG mice had metastases in the liver, lungs, and lymph nodes. Characterization of the NSG and nude mouse is necessary to study breast cancer brain metastasis in vivo. Here, we show that the 231BR cell line grew differently in NSG mice compared to nude mice. This work demonstrates the role that imaging can play toward credentialing these models that cannot be done with other in vitro or histopathologic methods alone.

biophysics↗

bioRxiv2019

Engineering self-homing circulating tumour cells as novel cancer theranostics

Purpose: New ways to target and treat metastatic disease are urgently needed. Tumor \"self-homing\" describes the recruitment of circulating tumor cells (CTCs) back to a previously excised primary tumor location, contributing to tumor recurrence, as well as their migration to established metastatic lesions. Recently, self-homing CTCs have been exploited as delivery vehicles for anti-cancer therapeutics in preclinical primary tumor models. However, the ability of CTCs to self-home and treat metastatic disease is largely unknown. Methods: Here, we employ molecular imaging to explore whether systemically-administered CTCs home to metastatic lesions and if CTCs armed with both a reporter gene and a cytotoxic prodrug gene therapy can be used to visualize and treat metastatic disease. Results: Bioluminescence imaging (BLI) performed over time revealed a remarkable ability of CTCs to home to primary and metastatic tumors throughout the body. Mice that received therapeutic CTCs had less BLI signal as well as less primary tumour burden than control mice. Preliminary data also showed self-homing therapeutic CTCs may be effective at treating disseminated breast cancer metastases. Conclusion: Using dual-luciferase BLI, this study demonstrates the noteworthy ability of experimental CTCs to home to disseminated breast cancer lesions. Moreover, by incorporating a prodrug gene therapy system into our self-homing CTCs, we show exciting progress towards effective and targeted delivery of gene-based therapeutics to treat both primary and metastatic lesions.

cancer biology↗

bioRxiv2019

Frequency and Distribution of Corneal Astigmatism and Keratometry Features: Methodology and Findings of the UK Biobank Study

PurposeTo describe corneal astigmatism in the UK Biobank population, to look for associations with other biometric variables and socio-demographic factors, and to report the proportion with abnormal keratometry and irregular astigmatism suggestive of pathological corneal ectasias such as keratoconus.\n\nMethodsCross-sectional data were obtained from UK Biobank (www.ukbiobank.ac.uk/). A subsample of 107,452 participants from UK communities had undergone an enhanced ophthalmic examination including autorefractor keratometry (Tomey RC 5000, Tomey Corp., Nagoya, Japan). After quality control and applying relevant exclusions, data on corneal astigmatism on 83,751 participants was available for analysis. Potential associations were tested through univariable regression and significant parameters carried forward for multivariable analysis.\n\nResultsIn a univariable analysis, the characteristics significantly protective against corneal astigmatism were gender (male), older age, darker skin colour and increased alcohol intake (all p<0.001). The parameters significantly associated with increased corneal astigmatism were older age at completion of full time education, use of UV protection and lower corrected visual acuity. After inclusion in the multivariable analysis, age, gender, age at completion of full time education, corrected visual acuity and skin colour remained significant (all p<0.001). Increased corneal astigmatism was also found to be significantly associated with amblyopia or strabismus. No individuals with abnormal keratometry or irregular astigmatism were reported.\n\nConclusionsThis analysis of associations with astigmatism in a large cohort of volunteers confirms previous associations including adverse associations with younger age and female gender, and identified novel associations including darker skin colour and frequency of alcohol intake. The highest risk group for corneal astigmatism were younger females of lighter skin colour, having completed full time education later, with higher logMAR corrected visual acuity. We also confirmed that corneal astigmatism is a high risk factor for amblyopia and strabismus. Finally since no cases of keratoconus were identified, this would suggest that simple keratometry indices may not be sufficient for population screening of keratoconus.

epidemiology↗