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) (original) (raw)
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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
Radiopharmaceuticals for renal studies: Evaluation of protein binding
Journal of Radioanalytical and Nuclear Chemistry, 1989
Determination of total in vitro protein binding was evaluated for the following radiopharmaceuticals:99mTc-diethylenetriaminepentaacetic acid (DTPA),99mTc-dimercaptosuccinic acid (DMSA),99mTc-glucoheptonate (GH) and99mTc-fosfomycin (PHO). For that they were incubated wtih human serum at 37°C. After three and sixty minutes of incubation, the bound fraction was evaluated by two different methods: gel filtration and precipitation with trichloroacetic acid (TCA). The percentage of the99mTc-kidney agents bound
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.
Pharmacokinetics and renal handling of 99mTc-labeled peptides
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2000
99mTc-labeled peptides, particularly those of a lipophilic nature, are often excreted through the hepatobiliary system, and the subsequent accumulation in the intestine may obscure receptor-mediated uptake in tumor sites in the pelvis. We have therefore explored the route and rate of excretion of a small series of Tc-labeled peptides to shed some light on the mechanisms that influence the clearance of these agents. Pharmacokinetic parameters, biodistribution, routes of elimination of 99mTc-complexes of 3 model tetrapeptides--namely, acetyl-N-Gly-Gly-Cys-Gly (AGGCG), acetyl-N-Ser-Ser-Cys-Gly (ASSCG), and acetyl-N-Gly-Gly-Cys-Lys (AGGCL)--were determined in rats in vivo. Renal handling of the complexes was studied in the perfused rat kidney. After intravenous injection, a relatively fast disappearance of the complexes from blood was found. Although the parameters of distribution in all 3 chelates were very similar, the elimination rate of 99mTc-AGGCG was higher than those of 99mTc-ASS...
Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells
Contrast Media & Molecular Imaging, 2018
Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. ese cells are usually labelled with 111 In or 99m Tc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. e most common compound in Europe is HMPAO that efficiently chelates 99m Tc. However, up to 20-40% of the complex is released from the cells in the first few hours. e aim of this study was to radiolabel a new compound, (S 3 CPh) 2 (S 2 CPh)-complex (SSS-complex) with 99m Tc and compare its binding kinetics and specificity for WBC with HMPAO. e SSS-complex was labelled with 99m Tc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99m Tc-SSS-complex and 99m Tc-HMPAO, respectively (p � ns). 99m Tc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99m Tc-SSS-complex than 99m Tc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p � 0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p � 0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p � ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSScomplex (10.3 ± 1.9% vs 21.3 ± 1.8%; p � 0.001). In conclusion, 99m Tc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99m Tc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.
Plasma protein binding of 99mTc-labeled hydrazino nicotinamide derivatized polypeptides and peptides
Nuclear Medicine and Biology, 2001
6-Hydrazinopyridine-3-carboxylic acid (HYNIC) constitutes one of the most attractive reagents to prepare 99m Tc-labeled polypeptides and peptides of various molecular weights in combination with two tricine molecules as coligands. Indeed, 99m Tc-HYNIC-conjugated IgG showed biodistribution of radioactivity similar to that of 111 In-DTPA-conjugated IgG. However, recent studies indicated significant plasma protein binding when the 99m Tc labeling procedure was expanded to low molecular weight peptides. In this study, pharmacokinetics of 99m Tc-HYNIC-conjugated IgG, Fab and RC160 using tricine were compared with their radioiodinated counterparts to evaluate this 99m Tc-labeling method. In mice, [ 99m Tc](HYNIC-IgG)(tricine) 2 and [ 99m Tc](HYNIC-Fab)(tricine) 2 showed persistent localization of radioactivity in tissues when compared with their 125 I-labeled counterparts. [ 99m Tc](HYNIC-IgG)(tricine) 2 eliminated from the blood at a rate similar to that of 125 I-labeled IgG, while [ 99m Tc](HYNIC-Fab)(tricine) 2 showed significantly slower clearance of the radioactivity than 125 I-labeled Fab. On size-exclusion HPLC analyses, little changes were observed in radiochromatograms after incubation of [ 99m Tc](HYNIC-IgG)(tricine) 2 in murine plasma. However, [ 99m Tc](HYNIC-Fab)(tricine) 2 and [ 99m Tc](HYNIC-RC160)(tricine) 2 demonstrated significant increases in the radioactivity in higher molecular weight fractions in plasma. Formation of higher molecular weight species was reduced when [ 99m Tc](HYNIC-RC160)(tricine) 2 was stabilized with nicotinic acid (NIC) to generate [ 99m Tc](HYNIC-RC160)(tricine)(NIC). [ 99m Tc](HYNIC-RC160)(tricine)(NIC) also demonstrated significantly faster clearance of the radioactivity from the blood than [ 99m Tc](HYNIC-RC160)(tricine) 2 . These findings suggested that one of the tricine coligands in 99m Tc-HYNIC-labeled (poly)peptides would be replaced with plasma proteins to generate higher molecular weight species that exhibit slow blood clearance. In addition, the molecular sizes of parental peptides played an important role in the progression of the exchange reaction of one of the tricine coligands with plasma proteins.
Pharmacokineticsand Renal Handling of 99@Tc-Labeled Peptides
2000
the incorporation of suitablepeptidesequencespermitsthemto exploit efficient routes of renal excretion,such as tubular secre tion, therebyoptimizingthe pattem of biodistribution of these radiopharmaceuticals. by on June 22, 2015. For personal use only. jnm.snmjournals.org Downloaded from J Nucl Med. Tc-Labeled Peptides 99m Pharmacokinetics and Renal Handling of http://jnm.snmjournals.org/content/41/1/177 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
Decreased renal uptake of 99mTc-DMSA in patients with tubular proteinuria
Pediatric Nephrology, 2009
Although technetium-99m-dimercaptosuccinic acid (99m Tc-DMSA) renal scans are widely used to evaluate renal tubular mass function, the mechanism by which renal uptake of DMSA occurs is still the subject of debate. Patients with various proximal tubular disorders show markedly decreased renal DMSA uptake, even when there is normal creatinine clearance. We measured the renal uptake of 99m Tc-DMSA 3 h after its injection in 13 patients with Dent disease or Lowe syndrome, both of which are typical proximal tubular disorders with defective megalin and cubilin-mediated endocytosis. Serial images of three patients were also obtained at 0.5, 1, 2 and 3 h postinjection. The correlations between renal uptake of 99m Tc-DMSA and creatinine clearance and the degrees of acidemia and tubular proteinuria were then evaluated. The renal uptake of 99m Tc-DMSA was markedly decreased in all patients, and the decreased uptake was detected in all serial images. In contrast, bladder radioactivity was higher than normal in all of the serial images when compared to renal radioactivity. Additionally, the uptake of 99m Tc-DMSA was inversely proportional to the amount of urine β 2-microglobulin. These results strongly suggest that DMSA is filtered in the glomeruli and subsequently undergoes megalin-and cubilin-mediated endocytosis in the proximal tubules.