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  • 1
    Electronic Resource
    Electronic Resource
    Characteristics and biological behaviour of 99mTc-labelled hydroxyacetyltriglycine, a potential alternative to 99mTc-MAG3 (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 1374-1379 
    Details
    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
    URL: http://dx.doi.org/10.1007/s002590050163
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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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  • 5
    Electronic Resource
    Electronic Resource
    Reduction of contamination risks during clinical studies with Technegas (1999)
    Springer
    European journal of nuclear medicine 26 (1999), S. 1349-1352 
    Details
    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).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050594
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