Examining the Feasibility of Quantifying Receptor Availability Using Cross-Modality Paired-Agent Imaging

Abstract Purpose The ability to noninvasively quantify receptor availability (RA) in solid tumors is an aspirational goal of molecular imaging, often challenged by the influence of non-specific accumulation of the contrast agent. Paired-agent imaging (PAI) techniques aim to compensate for this effect by imaging the kinetics of a targeted agent and an untargeted isotype, often simultaneously, and comparing the kinetics of the two agents to estimate RA. This is usually accomplished using two spectrally distinct fluorescent agents, limiting the technique to superficial tissues and/or preclinical applications. Applying the approach in humans using conventional imaging modalities is generally infeasible since most modalities are unable to routinely image multiple agents simultaneously. We examine the ability of PAI to be implemented in a cross-modality paradigm, in which the targeted and untargeted agent kinetics are imaged with different modalities and used to recover receptor availability. Procedures Eighteen mice bearing orthotopic brain tumors were administered a solution containing three contrast agents: (1) a fluorescent agent targeted to epidermal growth factor receptor (EGFR), (2) an untargeted fluorescent isotype, and (3) a gadolinium-based contrast agent (GBCA) for MRI imaging. The kinetics of all three agents were imaged for 1 h after administration using an MRI-coupled fluorescence tomography system. Paired-agent receptor availability was computed using (1) the conventional all-optical approach using the targeted and untargeted optical agent images and (2) the cross-modality approach using the targeted optical and untargeted MRI-GBCA images. Receptor availability estimates between the two methods were compared. Results Receptor availability values using the cross-modality approach were highly correlated to the conventional, single-modality approach (r = 0.94; p < 0.00001). Conclusion These results suggest that cross-modality paired-agent imaging for quantifying receptor availability is feasible. Ultimately, cross-modality paired-agent imaging could facilitate rapid, noninvasive receptor availability quantification in humans using hybrid clinical imaging modalities.

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The mechanism of the anionic coordination polymerization of isoprene

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19802391 ◽

1980 ◽

Vol 45 (9) ◽

pp. 2391-2399 ◽

Cited By ~ 1

Author(s):

Miroslav Kašpar ◽

Jiří Trekoval

Keyword(s):

Chromatographic Method ◽

Initial Period ◽

Reaction Scheme ◽

Polymerization Kinetics ◽

Coordination Polymerization ◽

Initial Concentration ◽

The Cross ◽

Gas Chromatographic Method ◽

Kinetics Of

The polymerization kinetics of isoprene (2-methyl-1,3-butadiene) in benzene with butyllithium as the initiator was investigated by the gas chromatographic method. After completion of the initial period of the reaction, its order with respect to the initial concentration of initiator is negative at the concentrations of the latter between 0.01 and 0.25 mol/l, and positive at higher concentrations. A reaction scheme has been suggested with respect to the "cross" association of butyllithium and of the "living" oligoisoprene.

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Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study

Nanomaterials ◽

10.3390/nano11051235 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1235

Author(s):

Xiaohui Nan ◽

Wenjia Lai ◽

Dan Li ◽

Jiesheng Tian ◽

Zhiyuan Hu ◽

...

Keyword(s):

Contrast Agent ◽

Magnetic Domain ◽

Bilayer Membrane ◽

The Body ◽

Mri Contrast Agent ◽

Mri Imaging ◽

Mri Contrast

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.

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Seasonality in the Cross Section of Stock Returns: The International Evidence

Journal of Financial and Quantitative Analysis ◽

10.1017/s0022109010000451 ◽

2010 ◽

Vol 45 (5) ◽

pp. 1133-1160 ◽

Cited By ~ 37

Author(s):

Steven L. Heston ◽

Ronnie Sadka

Keyword(s):

Stock Returns ◽

Cross Section ◽

Domestic Market ◽

Trading Strategies ◽

Global Risk ◽

Seasonal Predictability ◽

International Evidence ◽

Local Risk ◽

The Cross ◽

Highly Correlated

AbstractThis paper studies seasonal predictability in the cross section of international stock returns. Stocks that outperform the domestic market in a particular month continue to outperform the domestic market in that same calendar month for up to 5 years. The pattern appears in Canada, Japan, and 12 European countries. Global trading strategies based on seasonal predictability outperform similar nonseasonal strategies by over 1% per month. Abnormal seasonal returns remain after controlling for size, beta, and value, using global or local risk factors. In addition, the strategies are not highly correlated across countries. This suggests they do not reflect return premiums for systematic global risk.

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Diabetes, Obesity, and Inflammation: Impact on Clinical and Radiographic Features of Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052757 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2757

Author(s):

Braden Miller ◽

Hunter Chalfant ◽

Alexandra Thomas ◽

Elizabeth Wellberg ◽

Christina Henson ◽

...

Keyword(s):

Breast Cancer ◽

Imaging Techniques ◽

Growth Factor Receptor ◽

Breast Cancer Diagnosis ◽

Screening Mammography ◽

Imaging Modalities ◽

Conventional Imaging ◽

Obese Women ◽

Detection Rates ◽

Therapeutic Decision Making

Obesity, diabetes, and inflammation increase the risk of breast cancer, the most common malignancy in women. One of the mainstays of breast cancer treatment and improving outcomes is early detection through imaging-based screening. There may be a role for individualized imaging strategies for patients with certain co-morbidities. Herein, we review the literature regarding the accuracy of conventional imaging modalities in obese and diabetic women, the potential role of anti-inflammatory agents to improve detection, and the novel molecular imaging techniques that may have a role for breast cancer screening in these patients. We demonstrate that with conventional imaging modalities, increased sensitivity often comes with a loss of specificity, resulting in unnecessary biopsies and overtreatment. Obese women have body size limitations that impair image quality, and diabetes increases the risk for dense breast tis-sue. Increased density is known to obscure the diagnosis of cancer on routine screening mammography. Novel molecu-lar imaging agents with targets such as estrogen receptor, human epidermal growth factor receptor 2 (HER2), pyrimi-dine analogues, and ligand-targeted receptor probes, among others, have potential to reduce false positive results. They can also improve detection rates with increased resolution and inform therapeutic decision making. These emerg-ing imaging techniques promise to improve breast cancer diagnosis in obese patients with diabetes who have dense breasts, but more work is needed to validate their clinical application.

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Troponin T isoforms modulate calcium dependence of the kinetics of the cross-bridge cycle: studies using a transgenic mouse line

Archives of Biochemistry and Biophysics ◽

10.1016/s0003-9861(02)00370-3 ◽

2002 ◽

Vol 405 (2) ◽

pp. 241-246 ◽

Cited By ~ 11

Author(s):

Sarah M MacFarland ◽

Jian-Ping Jin ◽

Frank V Brozovich

Keyword(s):

Transgenic Mouse ◽

Troponin T ◽

Mouse Line ◽

Calcium Dependence ◽

Transgenic Mouse Line ◽

Cross Bridge ◽

The Cross ◽

Kinetics Of

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Monitoring ferumoxide-labelled neural progenitor cells and lesion evolution by magnetic resonance imaging in a model of cell transplantation in cerebral ischaemia

F1000Research ◽

10.12688/f1000research.2-252.v2 ◽

2014 ◽

Vol 2 ◽

pp. 252

Author(s):

Rachael A Panizzo ◽

David G Gadian ◽

Jane C Sowden ◽

Jack A Wells ◽

Mark F Lythgoe ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Contrast Agent ◽

Cerebral Ischaemia ◽

Mri Contrast Agent ◽

Lesion Volume ◽

Mri Imaging ◽

Resonance Imaging ◽

Protamine Sulphate

Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia could be better evaluated by monitoring in vivo migration and distribution of cells post-engraftment in parallel with analysis of lesion volume and functional recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but still poses several challenges. We show that combining the ferumoxide MRI contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled NPCs proliferated and differentiated normally in vitro, and upon grafting into the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over four weeks showed the development of a confounding endogenous hypointense contrast evolution at later timepoints within the lesioned tissue. This was at least partly due to accumulation within the lesion of macrophages and endogenous iron. Neither significant NPC migration, assessed by MRI and histologically, nor a reduction in the ischaemic lesion volume was observed in NPC-grafted brains. Crucially, while MRI provides reliable information on engrafted cell location early after an ischaemic insult, pathophysiological changes to ischaemic lesions can interfere with cellular imaging at later timepoints.

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Stress–response relationships related to ageing and death of orthodox seeds: a study comparing viability and RNA integrity in soya bean (Glycine max) cv. Williams 82

Seed Science Research ◽

10.1017/s0960258520000197 ◽

2020 ◽

Vol 30 (2) ◽

pp. 161-172

Author(s):

Christina Walters ◽

Margaret B. Fleming ◽

Lisa M. Hill ◽

Emma J. Dorr ◽

Christopher M. Richards

Keyword(s):

Degradation Kinetics ◽

Rna Degradation ◽

Soya Bean ◽

Rna Integrity ◽

Viability Loss ◽

Rna Integrity Number ◽

Oxidative Stresses ◽

Degradation Rates ◽

Highly Correlated ◽

Kinetics Of

AbstractCharacterizing non-lethal damage within dry seeds may allow us to detect early signs of ageing and accurately predict longevity. We compared RNA degradation and viability loss in seeds exposed to stressful conditions to quantify relationships between degradation rates and stress intensity or duration. We subjected recently harvested (‘fresh’) ‘Williams 82’ soya bean seeds to moisture, temperature and oxidative stresses, and measured time to 50% viability (P50) and rate of RNA degradation, the former using standard germination assays and the latter using RNA Integrity Number (RIN). RIN values from fresh seeds were also compared with those from accessions of the same cultivar harvested in the 1980s and 1990s and stored in the refrigerator (5°C), freezer (−18°C) or in vapour above liquid nitrogen (−176°C). Rates of viability loss (P50−1) and RNA degradation (RIN⋅d−1) were highly correlated in soya bean seeds that were exposed to a broad range of temperatures [holding relative humidity (RH) constant at about 30%]. However, the correlation weakened when fresh seeds were maintained at high RH (holding temperature constant at 35°C) or exposed to oxidizing agents. Both P50−1 and RIN⋅d−1 parameters exhibited breaks in Arrhenius behaviour near 50°C, suggesting that constrained molecular mobility regulates degradation kinetics of dry systems. We conclude that the kinetics of ageing reactions at RH near 30% can be simulated by temperatures up to 50°C and that RNA degradation can indicate ageing prior to and independent of seed death.

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The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.5.h2428 ◽

1997 ◽

Vol 273 (5) ◽

pp. H2428-H2435 ◽

Cited By ~ 17

Author(s):

Thomas Wannenburg ◽

Paul M. L. Janssen ◽

Dongsheng Fan ◽

Pieter P. De Tombe

Keyword(s):

Cardiac Muscle ◽

Maximum Rate ◽

Sarcomere Length ◽

Myosin Head ◽

Isometric Force ◽

Force Development ◽

Cross Bridge ◽

Average Slope ◽

The Cross ◽

Kinetics Of

We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 μm). The maximum rate of ATP consumption was 1.5 nmol ⋅ s−1 ⋅ μl fiber vol−1, which represents an estimated adenosinetriphosphatase (ATPase) rate of ∼10 s−1 per myosin head at 24°C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol ⋅ mN−1 ⋅ mm−1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.

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