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Greg M. Thurber - One of the best experts on this subject based on the ideXlab platform.
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tracking antibody distribution with near infrared fluorescent dyes impact of dye structure and degree of labeling on Plasma Clearance
Molecular Pharmaceutics, 2017Co-Authors: Cornelius Cilliers, Ian Nessler, Nikolas Christodolu, Greg M. ThurberAbstract:Monoclonal antibodies labeled with near-infrared (NIR) fluorophores have potential use in disease detection, intraoperative imaging, and pharmacokinetic characterization of therapeutic antibodies in both the preclinical and clinical setting. Recent work has shown conjugation of NIR fluorophores to antibodies can potentially alter antibody disposition at a sufficiently high degree of labeling (DoL); however, other reports show minimal impact after labeling with NIR fluorophores. In this work, we label two clinically approved antibodies, Herceptin (trastuzumab) and Avastin (bevacizumab), with NIR dyes IRDye 800CW (800CW) or Alexa Fluor 680 (AF680), at 1.2 and 0.3 dyes/antibody and examine the impact of fluorophore conjugation on antibody Plasma Clearance and tissue distribution. At 0.3 DoL, AF680 conjugates exhibited similar Clearance to unlabeled antibody over 17 days while 800CW conjugates diverged after 4 days, suggesting AF680 is a more suitable choice for long-term pharmacokinetic studies. At the 1.2 D...
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quantitative impact of Plasma Clearance and down regulation on glp 1 receptor molecular imaging
Molecular Imaging and Biology, 2016Co-Authors: Liang Zhang, Greg M. ThurberAbstract:Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of Plasma Clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and Plasma Clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow Plasma Clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.
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quantitative impact of Plasma Clearance and down regulation on glp 1 receptor molecular imaging
Molecular Imaging and Biology, 2016Co-Authors: Liang Zhang, Greg M. ThurberAbstract:Purpose Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of Plasma Clearance and receptor internalization on targeting efficiency in healthy B6 mice.
Flavio Gaspari - One of the best experts on this subject based on the ideXlab platform.
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iohexol Plasma Clearance simplified by dried blood spot dbs sampling to measure renal function in conscious mice
Scientific Reports, 2021Co-Authors: Ana Elena Rodriguezrodriguez, Sergio Luislima, Flavio Gaspari, Laura Diazmartin, Alejandro Jimenezsosa, Javier Donatecorrea, Maria Rosa Arnau, Alberto Ortiz, Esteban PorriniAbstract:There is no simple method to measure glomerular filtration rate (GFR) in mice, which limits the use of mice in models of renal diseases. We aimed at simplifying the Plasma Clearance of iohexol in mice, using dried blood spot (DBS) sampling in order to reduce the amount of blood taken for analysis. GFR was measured simultaneously by a reference method in total blood-as described before-and tested method using DBS in fifteen male and six female C57BL/6J mice. Total blood extraction was 50 μL for the reference methods and 25μL for the tested methods, distributed in 5 samples. The agreement of GFR values between both methods was analyzed with the concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). The agreement between both methods was excellent, showing a TDI = 8.1%, which indicates that 90% of the GFR values obtained with DBS showed an error ranging from - 8 to + 8% of the reference method; a CCC of 0.996 (CI: 0.992), reflecting high precision and accuracy and a CP of 94 (CI: 83), indicating that 6% of the GFR values obtained with DBS had an error greater than 10% of the method in blood. So, both methods are interchangeable. DBS represent a major simplification of GFR measurement in mice. Also, DBS improves animal welfare by reducing the total blood required and refining the procedure.
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a simple method to measure renal function in swine by the Plasma Clearance of iohexol
International Journal of Molecular Sciences, 2018Co-Authors: Sergio Luislima, Flavio Gaspari, Natalia Negrinmena, Fabiola Carrara, Alejandro Jimenezsosa, Consolacion Garciacontreras, Marta Vazquezgomez, Susana Astiz, Hugo Jimenezhernandez, A GonzalezbulnesAbstract:There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the Plasma Clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = −47.909 + (1.176xCL1) − (0.00063968xCL12). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials.
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iohexol Plasma Clearance simplified by dried blood spot testing
Nephrology Dialysis Transplantation, 2017Co-Authors: Sergio Luislima, Flavio Gaspari, Natalia Negrinmena, Fabiola Carrara, Laura Diazmartin, Alejandro Jimenezsosa, Federico Gonzalezrinne, Armando Torres, Esteban PorriniAbstract:Background Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the Plasma Clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. Methods We compared glomerular filtration rate (GFR) values assessed by DBS and the reference Plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and Plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI Results In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in Plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in Plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5% compared with the reference method. Conclusions We simplified the Plasma Clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community.
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iohexol Plasma Clearance for measuring glomerular filtration rate in clinical practice and research a review part 1 how to measure glomerular filtration rate with iohexol
Ndt Plus, 2016Co-Authors: Pierre Delanaye, Flavio Gaspari, Jonas Björk, Natalie Ebert, Toralf Melsom, Christophe Mariat, Etienne Cavalier, Anders Christensson, Ulf Nyman, Esteban PorriniAbstract:A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrowtherapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the onlyway to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol Plasma Clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research. (Less)
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iohexol Plasma Clearance for measuring glomerular filtration rate in clinical practice and research a review part 1 how to measure glomerular filtration rate with iohexol
Ndt Plus, 2016Co-Authors: Pierre Delanaye, Flavio Gaspari, Jonas Björk, Natalie Ebert, Toralf Melsom, Christophe Mariat, Etienne Cavalier, Anders Christensson, Ulf Nyman, Esteban PorriniAbstract:A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrowtherapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the onlyway to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol Plasma Clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.
Esteban Porrini - One of the best experts on this subject based on the ideXlab platform.
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iohexol Plasma Clearance simplified by dried blood spot dbs sampling to measure renal function in conscious mice
Scientific Reports, 2021Co-Authors: Ana Elena Rodriguezrodriguez, Sergio Luislima, Flavio Gaspari, Laura Diazmartin, Alejandro Jimenezsosa, Javier Donatecorrea, Maria Rosa Arnau, Alberto Ortiz, Esteban PorriniAbstract:There is no simple method to measure glomerular filtration rate (GFR) in mice, which limits the use of mice in models of renal diseases. We aimed at simplifying the Plasma Clearance of iohexol in mice, using dried blood spot (DBS) sampling in order to reduce the amount of blood taken for analysis. GFR was measured simultaneously by a reference method in total blood-as described before-and tested method using DBS in fifteen male and six female C57BL/6J mice. Total blood extraction was 50 μL for the reference methods and 25μL for the tested methods, distributed in 5 samples. The agreement of GFR values between both methods was analyzed with the concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). The agreement between both methods was excellent, showing a TDI = 8.1%, which indicates that 90% of the GFR values obtained with DBS showed an error ranging from - 8 to + 8% of the reference method; a CCC of 0.996 (CI: 0.992), reflecting high precision and accuracy and a CP of 94 (CI: 83), indicating that 6% of the GFR values obtained with DBS had an error greater than 10% of the method in blood. So, both methods are interchangeable. DBS represent a major simplification of GFR measurement in mice. Also, DBS improves animal welfare by reducing the total blood required and refining the procedure.
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iohexol Plasma Clearance simplified by dried blood spot testing
Nephrology Dialysis Transplantation, 2017Co-Authors: Sergio Luislima, Flavio Gaspari, Natalia Negrinmena, Fabiola Carrara, Laura Diazmartin, Alejandro Jimenezsosa, Federico Gonzalezrinne, Armando Torres, Esteban PorriniAbstract:Background Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the Plasma Clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. Methods We compared glomerular filtration rate (GFR) values assessed by DBS and the reference Plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and Plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI Results In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in Plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in Plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5% compared with the reference method. Conclusions We simplified the Plasma Clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community.
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iohexol Plasma Clearance for measuring glomerular filtration rate in clinical practice and research a review part 1 how to measure glomerular filtration rate with iohexol
Ndt Plus, 2016Co-Authors: Pierre Delanaye, Flavio Gaspari, Jonas Björk, Natalie Ebert, Toralf Melsom, Christophe Mariat, Etienne Cavalier, Anders Christensson, Ulf Nyman, Esteban PorriniAbstract:A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrowtherapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the onlyway to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol Plasma Clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research. (Less)
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iohexol Plasma Clearance for measuring glomerular filtration rate in clinical practice and research a review part 1 how to measure glomerular filtration rate with iohexol
Ndt Plus, 2016Co-Authors: Pierre Delanaye, Flavio Gaspari, Jonas Björk, Natalie Ebert, Toralf Melsom, Christophe Mariat, Etienne Cavalier, Anders Christensson, Ulf Nyman, Esteban PorriniAbstract:A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrowtherapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the onlyway to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol Plasma Clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.
Liang Zhang - One of the best experts on this subject based on the ideXlab platform.
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quantitative impact of Plasma Clearance and down regulation on glp 1 receptor molecular imaging
Molecular Imaging and Biology, 2016Co-Authors: Liang Zhang, Greg M. ThurberAbstract:Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of Plasma Clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and Plasma Clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow Plasma Clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.
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quantitative impact of Plasma Clearance and down regulation on glp 1 receptor molecular imaging
Molecular Imaging and Biology, 2016Co-Authors: Liang Zhang, Greg M. ThurberAbstract:Purpose Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of Plasma Clearance and receptor internalization on targeting efficiency in healthy B6 mice.
Sylvie Daminet - One of the best experts on this subject based on the ideXlab platform.
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Plasma Clearance of exogenous creatinine exo iohexol and endo iohexol in hyperthyroid cats before and after treatment with radioiodine
Journal of Veterinary Internal Medicine, 2008Co-Authors: I Van Hoek, Herve P Lefebvre, Siska Croubels, Kathelijne Peremans, H S Kooistra, Dominique Binst, Sylvie DaminetAbstract:Background: Glomerular filtration rate (GFR) can be measured by Clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. Hypothesis: Plasma Clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same Clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. Animals: Fifteen client-owned hyperthyroid cats. Methods: GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. Results: Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after 131I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. Conclusion and Clinical Importance: It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats.
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comparison and reproducibility of Plasma Clearance of exogenous creatinine exo iohexol endo iohexol and 51cr edta in young adult and aged healthy cats
Journal of Veterinary Internal Medicine, 2007Co-Authors: I Van Hoek, Eva Vandermeulen, Luc Duchateau, Herve P Lefebvre, Siska Croubels, Kathelijne Peremans, Ingeborgh Polis, Sylvie DaminetAbstract:Background: Important characteristics determining the usefulness of a method for glomerular filtration rate (GFR) measurement are convenience, availability, and reproducibility. Hypothesis: The use of different Plasma Clearance methods could lead to different results and differences in reproducibility. Animals: Twelve healthy cats: 6 young adult cats (age 7-12 months), and 6 aged cats (age 9-12 years) were included in this study. Methods: A cross-over design was used to compare the Plasma Clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), endo-iohexol (PenICT), and chromium-51 ethylenediaminetetraacetic acid (Cr-51-EDTA), and to investigate reproducibility of these methods. Cats of different ages were included to determine if differences in GFR in young adult versus aged cats would be detected with these methods. The PECCT, PexICT, and PenICT were performed in a combined manner. Plasma data were subjected to noncompartmental (creatinine, exo-iohexol, and endo-iohexol) or bicompartmental ((51)CrEDTA) analysis with a statistical moment approach. Area under the concentration-time curve was calculated using the trapezoidal rule with extrapolation to infinity. Statistical analyses were carried out using a random effects model. Results: Globally, the 4 methods differed significantly (P <.0001) in GFR assessment. Clearance of exo-iohexol and chromium-51 ethylenediaminetetra acetic acid (Cr-51 -EDTA) showed the highest and lowest reproducibility, respectively. Only Plasma Clearance of creatinine differed significantly between young adult and aged cats. Conclusion and Clinical importance: We found considerable differences in reproducibility of different GFR measurements. These findings should be taken into account not only in practice but also in future studies involving GFR measurement.