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  • 1
    Electronic Resource
    Electronic Resource
    First experience in healthy volunteers with technetium-99m l,l-ethylenedicysteine, a new renal imaging agent (1993)
    Springer
    European journal of nuclear medicine 20 (1993), S. 738-746 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00180902
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  • 2
    Electronic Resource
    Electronic Resource
    Complexes of technetium-99m with tetrapeptides containing one alanyl and three glycyl moieties (1996)
    Springer
    European journal of nuclear medicine 23 (1996), S. 40-48 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01736988
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  • 3
    Electronic Resource
    Electronic Resource
    Technetium-99m labelled human serum albumin for ventriculography: a comparative evaluation of six labelling kits (1993)
    Springer
    European journal of nuclear medicine 20 (1993), S. 465-472 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175158
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  • 4
    Electronic Resource
    Electronic Resource
    Technetium-99m mercaptoalbumin as a potential substitute for technetium-99m labelled red blood cells (1993)
    Springer
    European journal of nuclear medicine 20 (1993), S. 473-482 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175159
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