-
Nuclear Medicine and Biology 2018Equilibrium single-photon radionuclide imaging methods for assessing cardiac function and the integrity of the vascular system have long been in use for both clinical...
INTRODUCTION
Equilibrium single-photon radionuclide imaging methods for assessing cardiac function and the integrity of the vascular system have long been in use for both clinical and research purposes. However, positron-emitting blood pool agents that could provide PET equivalents to these (and other) clinical procedures have not yet been adopted despite technical imaging advantages offered by PET. Our goal was to develop a PET blood pool tracer that not only meets necessary in vivo biological requirements but can be produced with an uncomplicated and rapid synthesis method which would facilitate clinical translation. Herein, albumin labeled with fluorine-18 was synthesized using a one-pot method and evaluated in vitro and in vivo in rats.
METHODS
A ligand (NODA-Bz-TFPE), containing NODA attached to a tetrafluorophenylester (TFPE) via a phenyl linker (Bz), was labeled with aluminum fluoride (Al[F]F). Conjugation of the serum albumin with the ligand (Al[F]F-NODA-Bz-TFPE), followed by purification (size exclusion chromatography), yielded the final product (Al[F]F-NODA-Bz-RSA/HSA). In vitro stability was evaluated in human serum albumin by HPLC. Rat biodistributions and whole-body PET imaging over a 4 h time course were used for the in vivo evaluation.
RESULTS
This synthesis exhibited an overall radiochemical yield of 45 ± 10% (n = 30), a 50-min radiolabeling time, a radiochemical purity >99% and apparent stability up to 4 h in human serum. Blood had the highest retention of Al[F]F-NODA-Bz-RSA at all times with a blood half-life of 5.2 h in rats. Al[F]F-NODA-Bz-RSA distribution in most rat tissues remained relatively constant for up to 1 h, indicating that the tissue radioactivity content represents the respective tissue plasma volume. Dynamic whole-body PET images were in agreement with these findings.
CONCLUSIONS
A new ligand has been developed and radiolabeled with Al[F]F that allows rapid (50-min) preparation of fluorine-18 serum albumin in one-pot. In addition to increased synthetic efficiency, the construct appears to be metabolically stable in rats. This method could encourage wider use of PET to quantify cardiac function and tissue vascular integrity in both research and clinical settings.
Topics: Animals; Chemistry Techniques, Synthetic; Drug Stability; Fluorine Radioisotopes; Humans; Male; Positron-Emission Tomography; Radiochemistry; Rats; Serum Albumin; Tissue Distribution
PubMed: 29929114
DOI: 10.1016/j.nucmedbio.2018.05.004 -
Journal For Immunotherapy of Cancer Dec 2022As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual...
As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Therefore, serum albumin level could reflect IgG catabolic rate that directly impacts the clearance of therapeutic IgG antibodies. Through interrogating a large, clinically representative pan-cancer cohort of 1,479 ICB-treated patients, this study found that higher baseline albumin levels were significantly associated with stepwise improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) (<0.001), with the variability and reproducibility confirmed in 1,000 bootstrap-resampled cohorts. Furthermore, these findings were also confirmed in most subgroups defined by patient demographics, baseline characteristics, treatments, and cancer types, even in those with low ICB-responsive cancer types and low tumor mutation burden (TMB) (TMB≤10 mut/Mb) that most of which have not been approved by the US Food and Drug Administration (FDA) for ICB therapy. In summary, this study highlights the importance of pretreatment pharmacokinetic modeling for predicting ICB treatment outcomes. Based on serum albumin-an inexpensive, non-invasive, and easily accessible biomarker of IgG pharmacokinetics, we could take a step further towards optimizing ICB therapy.
Topics: United States; Humans; Immune Checkpoint Inhibitors; Serum Albumin; Reproducibility of Results; Antineoplastic Agents, Immunological; Mutation; Neoplasms; Treatment Outcome
PubMed: 36600664
DOI: 10.1136/jitc-2022-005670 -
Journal of Diabetes Science and... Mar 2015The measuring method for glycated albumin (GA) has been developed as a new glycemic control marker since the beginning of the 21st century. Since GA has an advantage in... (Review)
Review
The measuring method for glycated albumin (GA) has been developed as a new glycemic control marker since the beginning of the 21st century. Since GA has an advantage in reflecting glycemic status over a shorter period than hemoglobin A1c (HbA1c), much research and many reviews have been reported. However, so far there have been few reports on glycation sites based on the tertiary structure of human serum albumin (HSA) and the comparison of glycation rates between GA and HbA1c in detail. The present review discusses how the glycation sites of lysine residues in HSA are modified with glucose, whereas the glycation sites of lysine residues are located inside of HSA as well as the direct comparison of glycation rates between GA and HbA1c using human blood. Moreover, the most recent clinical researches on GA are described.
Topics: Biomarkers; Diabetes Mellitus; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Serum Albumin; Glycated Serum Albumin
PubMed: 25614014
DOI: 10.1177/1932296814567225 -
Current Alzheimer Research Feb 2010Results from clinical samples suggest low serum albumin may be associated with cognitive impairment, though evidence from population-based studies is inconclusive....
Results from clinical samples suggest low serum albumin may be associated with cognitive impairment, though evidence from population-based studies is inconclusive. Participants were 1,752 adults (699 men and 1,053 women) aged 65 years and over from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum albumin quartiles to cognitive impairment was modelled using logistic regression. Two hundred and twelve participants were cognitively impaired (68 men and 144 women). Odds ratios (95% confidence intervals) for cognitive impairment in the first (2.2-3.8 g/dl), second (3.9-4.0 g/dl), and third (4.1-4.3 g/dl) quartiles of serum albumin compared with the fourth (4.4-5.3 g/dl) were 2.5 (1.3-5.1), 1.7 (0.9-3.5), and 1.5 (0.7-2.9), after adjustment for age, sex, education and additional risk factors for cognitive impairment (p for linear trend = 0.002). A highly similar pattern of associations was observed for men and women. Our data provide new evidence to suggest that low serum albumin is independently associated with increased odds of cognitive impairment in the elderly population.
Topics: Aged; Aged, 80 and over; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Neuropsychological Tests; Odds Ratio; Serum Albumin
PubMed: 20205675
DOI: 10.2174/156720510790274392 -
International Journal of Molecular... Nov 2022Intravenous administration of crystalloid or colloid solutions is the most common intervention for correcting hypovolemia in intensive care unit patients. In critical... (Review)
Review
Intravenous administration of crystalloid or colloid solutions is the most common intervention for correcting hypovolemia in intensive care unit patients. In critical illness, especially sepsis and severe trauma, vascular wall permeability increases, and trans-endothelial escape of serum albumin, the major oncotic plasma constituent, contributes to the development of hypoalbuminemia and edema formation. The volume effects of intravenous human albumin solution exceed those of crystalloid solutions. If hypoalbuminemia is an effect moderator, the crystalloid-to-albumin ratio of fluid resuscitation volumes is not well characterized. Randomized controlled trials have confirmed that intravenous administration of human albumin solutions for volume resuscitation results in a lower net fluid balance compared with crystalloids, and smaller infusion volumes may be sufficient for hemodynamic stabilization when human albumin solutions are used. This narrative review summarizes the current evidence and conclusions drawn regarding the role of hypoalbuminemia in volume resuscitation. In the 'Saline versus Albumin Fluid Evaluation' study using 4% human albumin solution or saline, the saline-to-albumin ratio of study fluids was significantly higher in patients with baseline serum albumin concentrations of 25 g/L or less as compared to patients with baseline serum albumin concentrations of more than 25 g/L. In patients receiving renal replacement therapy, intravenous administration of 20-25% human albumin solution reduces intradialytic hypotension and improves fluid removal better than saline if serum albumin levels are similarly reduced. These data suggest that hypoalbuminemia acts as an effect moderator in volume resuscitation and plasma expansion with albumin solution. The volume effectiveness of intravenous human albumin solution in resuscitation appears to be greater when the serum albumin levels are low. In clinical situations, serum albumin concentrations per se may inform when and how to include intravenous albumin in fluid resuscitation if large amounts of crystalloids are needed, which requires further studies.
Topics: Humans; Hypoalbuminemia; Isotonic Solutions; Crystalloid Solutions; Infusions, Intravenous; Serum Albumin; Serum Albumin, Human
PubMed: 36430652
DOI: 10.3390/ijms232214175 -
International Journal of Molecular... Feb 2014Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs... (Review)
Review
Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug's pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA-drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.
Topics: Binding Sites; Humans; Kinetics; Models, Molecular; Molecular Structure; Pharmaceutical Preparations; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Serum Albumin
PubMed: 24583848
DOI: 10.3390/ijms15033580 -
Biosensors & Bioelectronics Feb 2024Developing highly selective and sensitive biosensors for diabetes management blood glucose monitoring is essential to reduce the health risks associated with diabetes....
Developing highly selective and sensitive biosensors for diabetes management blood glucose monitoring is essential to reduce the health risks associated with diabetes. Assessing the glycation (GA) of human serum albumin (HSA) serves as an indicator for medium-term glycemic control, making it suitable for assessing the efficacy of blood glucose management protocols. However, most biosensors are not capable of simultaneous detection of the relative fraction of GA to HSA in a clinically relevant range. Here, we report an effective miniaturised biosensor architecture for simultaneous electrochemical detection of HSA and GA across relevant concentration ranges. We immobilise DNA aptamers specific for the detection of HSA and GA on gold nanoislands (Au NIs) decorated screen-printed carbon electrodes (SPCEs), and effectively passivate the residual surface sites. We achieve a dynamic detection range between 20 and 60 mg/mL for HSA and 1-40 mg/mL for GA in buffer solutions. The analytical utility of our HSA and GA biosensor architectures are validated in mice serum indicating immediate potential for clinical applications. Since HSA and GA have similar structures, we extensively assess our sensor specificity, observing high selectivity of the HSA and GA sensors against each other and other commonly present interfering molecules in blood such as glucose, glycine, ampicillin, and insulin. Additionally, we determine the glycation ratio, which is a crucial metric for assessing blood glucose management efficacy, in an extensive range representing healthy and poor blood glucose management profiles. These findings provide strong evidence for the clinical potential of our biosensor architecture for point-of-care and self-assessment of diabetes management protocols.
Topics: Humans; Animals; Mice; Serum Albumin, Human; Serum Albumin; Glycated Serum Albumin; Blood Glucose; Glycation End Products, Advanced; Blood Glucose Self-Monitoring; Biosensing Techniques; Diabetes Mellitus
PubMed: 38039734
DOI: 10.1016/j.bios.2023.115876 -
Molecules (Basel, Switzerland) Sep 2022Artemisinin is known to bind to the main plasma protein carrier serum albumin (SA); however, there are no atomic level structural data regarding its binding mode with...
Artemisinin is known to bind to the main plasma protein carrier serum albumin (SA); however, there are no atomic level structural data regarding its binding mode with serum albumin. Herein, we employed a combined strategy of saturation transfer difference (STD), transfer nuclear Overhauser effect spectroscopy (TR-NOESY), STD-total correlation spectroscopy (STD-TOCSY), and Interligand Noes for PHArmacophore Mapping (INPHARMA) NMR methods and molecular docking calculations to investigate the structural basis of the interaction of artemisinin with human and bovine serum albumin (HSA/BSA). A significant number of inter-ligand NOEs between artemisinin and the drugs warfarin and ibuprofen as well as docking calculations were interpreted in terms of competitive binding modes of artemisinin in the warfarin (FA7) and ibuprofen (FA4) binding sites. STD NMR experiments demonstrate that artemisinin is the main analyte for the interaction of the extract with BSA. The combined strategy of NMR and docking calculations of the present work could be of general interest in the identification of the molecular basis of the interactions of natural products with their receptors even within a complex crude extract.
Topics: Artemisinins; Binding Sites; Biological Products; Complex Mixtures; Humans; Ibuprofen; Ligands; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Protein Binding; Serum Albumin; Serum Albumin, Bovine; Serum Albumin, Human; Warfarin
PubMed: 36144648
DOI: 10.3390/molecules27185912 -
International Journal of Molecular... Apr 2022Glycated human serum albumin (gHSA) undergoes conformational changes and unfolding events caused by free radicals. The glycation process results in a reduced ability of...
Quantification and Improvement of the Dynamics of Human Serum Albumin and Glycated Human Serum Albumin with Astaxanthin/Astaxanthin-Metal Ion Complexes: Physico-Chemical and Computational Approaches.
Glycated human serum albumin (gHSA) undergoes conformational changes and unfolding events caused by free radicals. The glycation process results in a reduced ability of albumin to act as an endogenous scavenger and transporter protein in diabetes mellitus type 2 (T2DM) patients. Astaxanthin (ASX) in native form and complexed with metal ions (Cu and Zn) has been shown to prevent gHSA from experiencing unfolding events. Furthermore, it improves protein stability of gHSA and human serum albumin (HSA) as it is shown through molecular dynamics studies. In this study, the ASX/ASX-metal ion complexes were reacted with both HSA/gHSA and analyzed with electronic paramagnetic resonance (EPR) spectroscopy, rheology and zeta sizer (particle size and zeta potential) analysis, circular dichroism (CD) spectroscopy and UV-Vis spectrophotometer measurements, as well as molecular electrostatic potential (MEP) and molecular docking calculations. The addition of metal ions to ASX improves its ability to act as an antioxidant and both ASX or ASX-metal ion complexes maintain HSA and gHSA stability while performing their functions.
Topics: Circular Dichroism; Coordination Complexes; Humans; Ions; Molecular Docking Simulation; Protein Binding; Serum Albumin; Serum Albumin, Human; Xanthophylls
PubMed: 35563162
DOI: 10.3390/ijms23094771 -
Biological & Pharmaceutical Bulletin Apr 2009Recombinant technology allows engineering and production of proteins with desirable properties. Human serum albumin has been developed with recombinant technology, and... (Review)
Review
Recombinant technology allows engineering and production of proteins with desirable properties. Human serum albumin has been developed with recombinant technology, and thus plays an increasing role as a drug carrier in the clinical setting. Genetic variations usually occur on the surface of the protein, and do not impose significant effects on the conformation of albumin. However, binding of fatty acids by genetic variants is affected according to the location of the mutation. Albumin undergoes three major posttranslational modifications, namely, oxidation, glycation, and S-nitrosylation. This review gives an account of the different posttranslational modifications that should be taken into consideration when designing albumin mutant analogues with desirable pharmaceutical properties.
Topics: Genetic Variation; Humans; Models, Molecular; Protein Processing, Post-Translational; Serum Albumin
PubMed: 19336879
DOI: 10.1248/bpb.32.527