Radiopharmaceuticals for renal studies: Evaluation of protein binding (original) (raw)

In vivo and i n vitro 99mTc-protein bound of renal agents: 99mTc-prylidinomethyltetracycline ( 99mTc-Sn-Pmt) and 99mTc-Sn-Gluco-ene-diolate ( 99mTc-Gluco)

Journal of Saudi Chemical Society, 2010

Protein binding affects tissue distribution, plasma clearance and uptake of renal radiopharmaceuticals. The 99m Tc bound to plasma protein after incubation 99m Tc-Gluco-ene-diolate (99m Tc-Sn-Gluco) agent or 99m Tc-prylidinomethyl-tetracycline (99m Tc-Sn-PMT) agent with plasma protein. It was observed that the protein bound to 99m Tc is lesser extent with (99m Tc-Sn-Gluco) agent than with the 99m Tc-PMT agent. 99m Tc-Sn-PMT is excreted more rapidly than 99m Tc-Sn-Gluco. On the other hand the percentage binding to protein seems to depend on the origin of the protein and or the type of protein (human or animal). However lower human protein binding or higher protein binding were observed with 99m Tc-Sn-Gluco or with 99m Tc-Sn-PMT, respectively compared with the binding to rat protein. The unbroken down of the chemical form of the origin of these two agents and the highest of 99m Tc-Sn-Gluco remained as origin in urine indicate that 99m Tc-Sn-Gluco are more stable than 99m Tc-Sn-PMT. Concerning the type of protein binding to 99m Tc-Sn-PMT or to 99m Tc-Sn-Gluco, it was observed that Human Plasma Protein is greater binding than Human serum protein or than IgG.

Binding of Diagnostic Radiopharmaceuticals to Human Serum Albumin by Sequential and Equilibrium Dialysis

Journal of Nuclear Medicine, 1982

The side chains of amino acids on protein molecules possess functional groups for formation of association complexeswith a variety ofdrugs and metal chelates (1â€"3). Although serum-protein binding ofradiopharmaceuticals plays a direct role in the metab olism, the rate of blood clearance, and the apparent volume of distribution, no systematic and quantitative studies of protein binding of radiopharmaceuticals had been reported. Since serum J Nucl Med. Mrinal K. Dewanjee and Equilibrium Dialysis Binding of Diagnostic Radiopharmaceuticals to Human Serum Albumin by Sequential http://jnm.snmjournals.org/content/23/8/753.citation This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

Equilibrium Dialysis and Ultrafiltration Compared for Determining the Protein Binding Rates of 99mTc-DTPA

2018

Diethylene triaminopentaacetic acid (99m Tc-DTPA) is one of the technetium radiopharmaceuticals mostly used in renal imaging for evaluation of glomera filtration rate. The 99m Tc-DTPA binding rates on plasma proteins was investigated using two useful and reproducible methods. Equilibrium Dialysis (ED) and Ultrafiltration (UF) are described and there are performances compared. 99m Tc-DTPA binds strongly to Human Serum (HS) than to Human Serum Albumin (HSA). In our assay, using UF technique, we found the binding rates were in HS 48.72 % ±2.58 and 51 % ±1.43 for respectively two 99m Tc-DTPA concentrations [1mg/L] and [2mg/L]. Using ED method we found the binding rates were in HS 11.22 % ±2.17 and 14.94 % ±2.30 for respectively two 99m Tc-DTPA concentrations [1mg/L] and [2mg/L]. Moreover, According to HSA concentrations, the 99m Tc-DTPA binding rates increase using both techniques.

Evaluation of 99mtechnetium-radiopharmaceutical binding to blood elements using different trichloroacetic acid concentrations

The Yale Journal of Biology and Medicine, 1996

Secure determination of the binding of 99mTc-radiopharmaceuticals to plasma (P) and blood cell (BC) constituents can help to understand the biodistribution of radiophamaceuticals. The reported precipitation studies of blood with radiopharmaceuticals have shown that the results can not be easily compared between studies. We decided to determine the "gold standard" concentration of trichloroacetic acid (TCA) to evaluate the binding to blood elements for several radiopharmaceuticals used in routine nuclear medicine. We have studied phytic (99mTc-PHY), diethylenetriaminepentaacetic (99mTc-DTPA), glucoheptonic (99mTc-GHA) and dimercaptosuccinic (99mTc-DMSA) acids. Blood was incubated with radiopharmaceuticals, centrifuged and P and BC separated. Samples of P and BC were also precipitated with TCA concentrations (20.0, 10.0, 5.0, 1.0, 0.5 and 0.1 percent) and soluble (SF) and insoluble fractions (IF) were isolated. The percent radioactivity (percent rad) in IF-P depends on TCA c...

The interactions of99mTc phosphorus radiopharmaceuticals and human serum proteins

Journal of Radioanalytical Chemistry, 1982

Dialysis and precipitation methods have been used to study the binding affinity of selected technetium-99m phosphorus radiopharmaceuticals to human serum proteins. The binding affinities of three different 99 mTc bone imaging agents were found to be inversely related to their respective clearance rates from blood in vivo. The binding order showed 99 mTcPP i > 99 mTcHEDP > 99 mTcMDP. The 99 mTc phosphorus radiopharmaceuticals were bound primarily to alpha globulins. The results suggest that the binding of ~ 9 mTc phosphorus radiopharmaceuticals to human serum proteins in blood is largely determined by their affinities to the alpha globulins.

Drug interaction with radiopharmaceuticals: a review

Brazilian Archives of Biology and Technology, 2005

Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.

Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules

Molecules, 2020

Affibody molecules are the most studied class of engineered scaffold proteins (ESPs) in radionuclide molecular imaging. Attempts to use affibody molecules directly labelled with radiometals for targeted radionuclide therapy were hampered by the high uptake and retention of radioactivity in kidneys. Several promising strategies have been implemented to circumvent this problem. Here, we investigated whether a pharmacological approach targeting different components of the reabsorption system could be used to lower the uptake of [99mTc]Tc-ZHER:2395 affibody molecule in kidneys. Pre-injection of probenecid, furosemide, mannitol or colchicine had no influence on activity uptake in kidneys compared to the control group. Mice pre-injected with maleate and fructose had 33% and 51% reduction in the kidney-associated activity, respectively, compared to the control group. Autoradiography images showed that the accumulation of activity after [99mTc]Tc-ZHER2:2395 injection was in the renal cortex...

Usage of radiopharmaceuticals in the development of pharmaceutical drug delivery systems: validation of [99mTc]DTPA and [99mTc]ECD

European Journal of Pharmaceutics and Biopharmaceutics, 2004

Tablets containing drugs of different lipophilicity, ranitidine and cinarizine, and placebo were prepared and their in vitro behaviour was studied by dissolution and disintegration tests. [ 99m Tc]Diethylenetriamine-pentaacetic acid ([ 99m Tc]DTPA) and [ 99m Tc]ethyl cysteinate dimer ([ 99m Tc]ECD) were used as tracers of the process. Both of them were added to tablets during wet granulation. Dissolution and disintegration profiles were assessed at different pH values (1, 4 and 7). Radioactivity was evaluated in filtered samples and scintigraphic studies were carried out in gamma camera. Stability in dissolution media was confirmed for both tracers under these conditions. Dissolution and disintegration velocity constants were calculated. [ 99m Tc]DTPA proved to be an appropriate tracer for polar drugs such as ranitidine. Nevertheless, it was not a suitable tracer for lipophilic active drugs such as cinarizine. On the other hand, the most lipophilic tracer, [ 99m Tc]ECD, exhibited the opposite behaviour. Scintigraphic studies of the disintegration process did not show significant differences between placebos and tablets containing active drugs. As disintegration is a physical process it does not discriminate between chemical differences in tablet formulations. Both methods complement each other because the dissolution process can be followed when a suitable radiotracer is chosen according to the physicochemical characteristics of the active drug. q

Estimating Binding Capability of Radiopharmaceuticals by Cell Culture Studies

International Journal of Medical Nano Research, 2016

Radiopharmaceuticals have applications in biologic research, drug discovery, diagnosis of human disease and molecular therapeutics for a wide variety of medical conditions. With the increasingly central role of radiotracers for non-invasive imaging of animal models and human research, small animal imaging centers are likely to have a growing interest in development of radiopharmaceutical science. Although animal experiments are giving the most valuable information about the drug behavior in the biological system. Also every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Use of cell culture techniques play a key role in new drug development studies by giving information about receptor interaction, drug uptake/efflux or interaction with other cellular receptors and cellular metabolism. This review will focus on how cell culture techniques are able to use to estimate the uptake of developed radiopharmaceutical by targeted receptor-bearing cells.

Interaction of 99mTc-radiopharmaceuticals with transport proteins in human blood

Nuclear Medicine and Biology, 1993

Interaction of a series of 99"Tc-radiopharmaceuticals with human blood proteins was investigated from two aspects: total protein binding, and specificity of binding to certain classes of proteins. After in vitro labelling of human sera with %Tcradiopharmaceuticals, total protein binding was determined for thirteen 99"Tc-compounds