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  • 1
    ISSN: 1619-7089
    Keywords: Technetium-99m l,l-ethylenedicysteine ; Renal function ; Healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Animal studies have indicated that technetium-99m l,l-ethylenedicysteine (99mTc-l,l-EC) may be a promising tracer agent for renal function studies. We have performed a paired study with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and 99mTc-l,l-EC in six male volunteers. In both cases, iodine-131-labelled o-iodohippurate was co-injected as an internal biological standard. The analog images between 0 and 30 min p.i. were of identical diagnostic value for both tracer agents. The two renograms were similar in all volunteers. The mean 1-h plasma clearance for 99mTc-MAG3 and 99 mTc-l,l-EC was significantly different, respectively 382.9 ± 17.1 ml/min per 1.73 m2 versus 460.2 ± 47.7 ml/min per 1.73 m2 (P〈0.003). The urinary excretion after 30 min p.i. was 69.4% ± 5.6% of the injected dose for 99mTc-MAG3 versus 66.5% ± 2.5% for 99mTc-l,l-EC (P〉0.05) and after 60 min p.i. respectively 83.1% ± 3.9% versus 79.8 % ± 4.3 % (P 〉 0.05). 99mTc-l,l-EC has a very low plasma protein binding (31% ± 6.8%) as compared to 99mTc-MAG3 (88% ± 5.2%) and a larger volume of distribution. Although the exact mechanism responsible for the high plasma clearance of 99mTc-l,l-EC is not yet fully known, we conclude that this new agent merits further clinical evaluation in patients to establish its value as a renal radiopharmaceutical.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-7089
    Keywords: Technetium-99m-L,L-ethylene dicysteine ; Technetium-99m-mercaptoacetyltriglycine ; Renal disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC), a new renal imaging agent, was introduced as an alternative to99mTc-mercaptoacetyltriglycine (MAG3). This radiopharmaceutical can be easily labelled at room temperature and has high radiochemical purity and long stability. The aim of this study was to gain clinical experience in using99mTc-L,L-EC in normal volunteers and patients. The clearance of this radiopharmaceutical was compared with that of iodine-131ortho-iodohippurate (OIH) in five healthy volunteers. In addition, conventional renogram and whole-body distribution of99mTc-L,L-EC (40 min and 3 h post-injection) were evaluated in these subjects. Subsequently, ten patients with suspected obstructive nephropathy, four with renovascular disorders and two in acute renal failure were imaged. In five patients with impaired renal function both99mTc-MAG3 and99mTc-L,L-EC studies were performed. In each case the scintigraphic images and time/activity curves were evaluated and various semiquantitative parameters calculated and compared. No adverse effects were noted during and after99mTc-L,L-EC scintigraphy. The mean clearance values for99mTc-L,L-EC and131I-OIH in volunteers were 504 and 663 ml/min respectively. The total plasma clearance of99mTc-L,L-EC was about 75.8% of the131I-0IH value. In volunteers the parenchymal transit time index, whole kidney transit time index and mean parenchymal transit time for99mTc-L,L-EC were 63 s, 124 s and 175 s respectively. The mean time to peak activity was 235 s and the time from peak to 50% of peak activity was 402 s. In all patients the results of scintigraphy were concordant with clinical findings and subsequently influenced patient management. Furthermore,99mTc-L,L-EC scintigraphy provided high-quality images similar to those obtained with99mTc-MAG3, even at low glomerular filtration rates (18 ml/min). It is concluded that99mTc-L,L-EC has excellent imaging characteristics similar to99mTc-MAG3 and excretion properties similar to OIH. This radiopharmaceutical can be used routinely to evaluate patients with renal disorders.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1619-7089
    Keywords: Key words: Hydroxyacetyltriglycine ; Mercaptoacetyltriglycine ; Labelling characteristics ; Biological behaviour ; Biodistribution studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Substitution of the oxidation-sensitive thiol function of mercaptoacetyltriglycine (MAG3) by a hydroxyl group yields a tetraligand (hydroxyacetyltriglycine or HAG3) which is almost insensitive to oxidation and has the advantage over MAG3 that it can be stored safely without protection of the alcohol function. We found that deprotected HAG3 could be directly labelled at alkaline pH (pH≥11.5) and room temperature in high yield (〉95%). Results of electrophoresis experiments suggested a comparable structure for 99mTc-HAG3 and 99mTc-MAG3, namely binding of an oxotechnetium(V)core via three deprotonated amides and a deprotonated hydroxyl group. Biodistribution studies in mice at 10 min and 30 min p.i. showed a slightly higher urinary excretion, a faster renal transit and a significantly lower hepatobiliary handling for 99mTc-HAG3 than for 99mTc-MAG3. In a baboon, the 1-h plasma clearance of 99mTc-HAG3 was clearly higher than that of 99mTc-MAG3. Its plasma protein binding was in the same order as that of Hippuran and much lower than that of 99mTc-MAG3. Evaluation in a human volunteer confirmed the favourable biological characteristics of 99mTc-HAG3, namely a rapid renal excretion, a high 1-h plasma clearance and a negligible hepatobiliary handling. The results indicate that 99mTc-HAG3 may be an easy-to-prepare and practical substitute for 99mTc-MAG3 with improved renal excretion characteristics.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1619-7089
    Keywords: Technetium-99m mercaptoacetylglycylalanylglycine-DA ; Technetium-99m mercaptoacetyltriglycine ; Mercaptoacetyltripeptides ; Renal tracer agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During a study of C-methyl derivatives of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) it was found that the isomer of 99mTc-mercaptoacetylgly-cyl-D-alanylglycine (99m-TC-MAGAG-DA) is superior to 99mTc-MAG3 with regard to its renal excretion characteristics in both mice and the baboon. We have now compared the renal handling of 99mTc-MAGAG-DA and 99mTc-MAG3 in 6 healthy volunteers in a paired study. Renograms of 99mTc-MAGAG-DA show a shorter time to renal maximum and a lower residual renal activity at 30 min post-injection (p.i.). The urinary excretion of 99mTc-MAGAG-DA is higher at both 30 and 60 min p.i. The plasma concentration of 99mTc-MAGAG-DA is lower than that of 99mTc-MAG3 at each moment up to 60 min p.i., and the plasma clearance is accordingly higher. It is concluded that 99mTc-MAGAG-DA is excreted more efficiently than 99mTc-MAG3, but the preparation of 99mTc-MAGAG-DA requires a HPLC purification step, and this limits its practical clinical usefulness.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 23 (1996), S. 40-48 
    ISSN: 1619-7089
    Keywords: Technetium-99m tetrapeptides ; Renal tracer agent ; Technetium-99m mercaptoacetyltriglycine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, we have shown that tetrapeptides can be efficiently labelled with technetium-99m by direct labelling at alkaline pH. Tetrapeptides can be considered derivatives of mercaptoacetyltriglycine (MAG3) in which the mercaptoacetyl moiety is replaced by an amino acid residue. In view of the interesting biological properties of some C-methyl substituted derivatives of99mTc-MAG3, we have now synthesised and evaluated the complexes of99mTc with tetrapeptides containing three glycyl (G) moieties and oned- orl-alanyl (A) moiety. In mice,99mTc-l-GAGG,99mTc-d-GGAG and99mTc-l-GGAG showed a rapid and high renal excretion, comparable to that of99mTc-MAG3. Renal handling was somewhat reduced for isomersd andl of99mTc-AGGG and99mTc-d-GAGG and markedly inferior for99mTc-l-GGGA and99mTc-d-GGGA. In the baboon,99mTc-l-AGGG,99mTc-d-AGGG and99mTc-l-GAGG showed a comparable or even higher 1-h plasma clearance than99mTc-MAG3.99mTc-d-GAGG,99mTc-l-GGAG and99mTc-d-GGAG were characterised by a lower plasma clearance and the clearance of99mTc-l-GGGA and99mTc-d-GGGA was remarkably low. The three99mTc-labelled tetrapeptides with the highest plasma clearance in a baboon were compared with99mTc-MAG3 in a human volunteer.99mTc-l-AGGG and99mTc-l-GAGG had a roughly similar plasma clearance as99mTc-MAG3. The clearance of99mTc-d-AGGG was significantly lower and liver uptake was clearly visible with this compound. Left kidney renograms of99mTc-l-AGGG and99mTc-d-AGGG indicated moderate kidney accumulation. On the other hand, the renogram obtained after injection of99mTc-l-GAGG had an excellent shape and the maximum kidney concentration was slightly higher than for99mTc-MAG3. These results show the importance of the position of the methyl substituent on the99mTc-tetrapeptide with respect to its biological behaviour.
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  • 6
    ISSN: 1619-7089
    Keywords: Technetium-99m labelled human serum albumin ; Labelling kit ; Ventriculography ; Blood pool agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study we have compared the characteristics of six labelling kits for the preparation of technetium-99m labelled human serum albumin (99mTc-HSA) and evaluated the usefulness of the various 99mTc-HSA preparations as blood pool tracer agents. The amount of the principal ingredients, i.e. HSA and stannous ions, varies largely between the studied kits and this is probably a reason for the observed differences in the labelling rate. Analysis of the reaction mixtures after labelling of the respective kits with 99mTc showed in each preparation the presence of four to five radioactive components in variable relative amounts. The retention time of the main component on size-exclusion high-performance liquid chromatography (SEC-HPLC) was identical for all preparations. Biodistribution of the HPLC-isolated fractions was studied in mice. The components with the shortest and longest retention times on HPLC show poor retention in the plasma. The three intermediate fractions, including the principal peak, are initially retained relatively well in the blood (60%–70% of the injected dose after 10 min), but clearly to a lower degree than iodine-125 labelled HSA. Moreover, they diffuse out of the vascular compartment at a much higher rate than 125I-HSA. The biological behaviour of the main component of the various preparations was clearly different, despite the identical retention time on SEC-HPLC. Study of the total preparations in mice and a rabbit showed that two of them are cleared rapidly from the blood and cannot be considered valuable blood pool tracers. Diffusion of the other preparations out of the blood is slower but also considerable and compromises their use for ventriculography.
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  • 7
    ISSN: 1619-7089
    Keywords: 99mTc-labelled human serum albumin ; 99mTc-mercaptoalbumin ; Ventriculography ; 99mTc-labelled erythrocytes ; 99mTc-DMP-HSA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Technetium-99m labelled red blood cells (99mTc-RBCs) are far superior to 99mTc-labelled human serum albumin (99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical 99mTc-mercaptoalbumin with long retention in the vascular system, that could replace 99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with 99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure 99mTc-mercaptoalbumin. Stable 99mTc-mercaptoalbumin complexes could be formed in 90%–95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25: 1 ratio and deprotection with NH2OH. The stability of the resulting 99mTc-mercaptoacetyl-albumin (99mTc-MAHSA) and 99mTc-dimercaptopropionyl-albumin (99mTcDMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional 99mTc-HSA preparations. 99mTc-DMP-HSA approaches the behaviour of 125I-HSA quite well in both animal species. A preliminary study with 99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of 99mTc-RBCs and clearly higher than that of a common 99mTc-HSA preparation. The results indicate that these 99mTc-mercaptoalbumins and especially 99mTc-DMP-HSA are very promising as a practical alternative to 99mTc-RBCs.
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  • 8
    ISSN: 1619-7089
    Keywords: Technetium-99m 2,3-dimercaptopropionylhuman serum albumin ; Ventriculography ; Technetium-99m-labelled red blood cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations — obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 — were tested in a volunteer and compared to 99mTcRBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle. However, a slightly higher liver uptake was seen with 99mTc-DMP-HSA 16:1, whereas the liver uptake of 99mTc-DMP-HSA 8:1 and 99mTc-RBCs was the same. These first results suggest that 99mTc-DMP-HSA, and in particular 99mTc-DMP-HSA 8:1, could be used for ventriculography as a practical and reliable alternative to 99mTc-RBCs.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 26 (1999), S. 1349-1352 
    ISSN: 1619-7089
    Keywords: Key words: Technegas ; Contamination ; Lung ventilation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. During patient studies with the Technegas equipment in our department, we regularly detected small to considerable contaminations of the operator and in the area surrounding the apparatus. These contaminations were found to be of different origin: residual activity in the tubing from the apparatus to the patient which diffuses after deconnection, residual activity and small particles of the destroyed carbon crucible in the apparatus which are dispersed during opening of the door of the gas preparation chamber, leakage at the patient site during studies in uncooperative patients and a dysfunctioning valve inside the apparatus. To reduce the contamination risks, we made some adaptations to the apparatus. In the first place, the dysfunctioning valve was replaced. In addition, a powerful air exhaust pump with an efficient filter was installed. It was connected with (1) a newly installed transparent box in front of the door of the gas preparation chamber, (2) a dome on a flexible arm which can be positioned above the patient’s face during the examination and (3) a nipple on which the mouthpiece can be placed after the study. After these adaptations, a study showed the absence of measurable contamination on the clothing of the personnel handling the apparatus. Occasionally, considerable contamination was still measured on the gloves worn during filling of the carbon boat with generator eluate, but only small contaminations (up to 9.25 kBq) were measured on the mouthmask worn by the operator during administration of the Technegas. This results in a maximum effective dose equivalent fromactivity deposited in the lungs of 0.008 µSv per study. The total body dose of the operator from external radiation for one Technegas examination was determined to be 2 µSv. The highest dose rate was measured during filling of the crucible (0.2 mSv/h).
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  • 10
    ISSN: 1619-7089
    Keywords: Key words: Alzheimer’s disease ; Diagnosis ; Congo red ; Chrysamine G ; Technetium-99m
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Chrysamine G (CG), an analogue of Congo red, is known to bind in vitro to the β-amyloid protein (Aβ 10-43) and to homogenates of several regions of the brain of Alzheimer’s disease (AD) patients. We synthesised a conjugate of 2-(acetamido)-CG with a bis-S-trityl protected monoamide-monoaminedithiol (MAMA-Tr2) tetraligand, which was efficiently deprotected and labelled with a 75% yield with technetium-99m, to obtain 99mTc-MAMA-CG. In mice, 99mTc-MAMA-CG was cleared mainly by the hepatobiliary system, resulting in a fast blood clearance. Brain uptake of 99mTc-MAMA-CG was low. Co-injection with the blood pool tracer iodine-125 human serum albumin (125I-HSA) demonstrated a brain/blood activity ratio for 99mTc-MAMA-CG that was significantly higher than that for 125I-HSA (t test for dependent samples, P〈0.02), indicating the ability of 99mTc-MAMA-CG to cross the blood-brain barrier. In vitro autoradiography demonstrated pronounced binding of 99mTc-MAMA-CG to β-amyloid deposits in autopsy sections of the parietal and occipital cortex of an AD patient as compared with controls. Adding 10 µM Congo red during incubation displaced the binding of 99mTc-MAMA-CG. Congo red staining and autoradiography identified the same lesions. 99mTc-MAMA-CG seems to bind selectively to β-amyloid deposition in human brain parenchyma and blood vessels in vitro and thus might be a lead compound for further development of a useful tracer agent for the in vivo diagnosis of Alzheimer’s disease.
    Type of Medium: Electronic Resource
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