An assessment study involving the use of the transglutaminase (TGase) conjugation method and the nitride-technetium-99m labelling on a bis(thiosemicarbazone) (BTS) bifunctional chelating agent is presented. The previously described chelator diacetyl-2-(N⁴-methyl-3-thiosemicarbazone)-3-(N⁴-amino-3-thiosemicarbazone), H₂ATSM/A, has been functionalized with 6-aminohexanoic acid (ε-Ahx) to generate the bifunctional chelating agent diacetyl-2-(N⁴-methyl-3-thiosemicarbazone)-3-[N⁴-(amino)-(6-aminohexanoic acid)-3-thiosemicarbazone], H₂ATSM/A-ε-Ahx (1), suitable for conjugation to glutamine (Gln) residues of bioactive molecules via TGase. The feasibility of the TGase reaction in the synthesis of a bioconjugate derivative was investigated using Substance P (SP) as model peptide. Compounds 1 and H₂ATSM/A-ε-Ahx-SP (2) were labelled with nitride-technetium-99m, obtaining the complexes [^99mTc][Tc(N)(ATSM/A-ε-Ahx)] (^99mTc1) and [^99mTc][Tc(N)(ATSM/A-ε-Ahx-SP)] (^99mTc2). The chemical identity of ^99mTc1 and ^99mTc2 was confirmed by radio/UV-RP-HPLC combined with ESI-MS analysis on the respective carrier-added products ^99g/99mTc1 and ^99g/99mTc2. The stability of the radiolabelled complexes after incubation in various environments was investigated. All the results were compared with those obtained for the corresponding ⁶⁴Cu-analogues ⁶⁴Cu1 and ⁶⁴Cu2. The TGase reaction allows the conjugation of 1 with the peptide, but it is not highly efficient due to instability of the chelator in the required conditions. The SP-conjugated complexes are unstable in mouse and human sera. However, indeed the BTS system can be exploited as nitride-technetium-99m chelator for highly efficient technetium labelling, thus making compound 1 worthy of further investigations for new targeted technetium and copper radiopharmaceuticals encompassing Single Photon Emission Computed Tomography and Positron Emission Tomography imaging.

提出了一项评估研究，涉及使用转谷氨酰胺酶（TGase）偶联方法和双（硫代半脲酮）（BTS）双功能螯合剂上的氮化物-tech-99m标记。先前描述的螯合剂二乙酰基-2-（N ^4-甲基-3-硫代半碳酮）-3-（N ^4-氨基-3-硫代半碳酮）H ₂ ATSM / A已通过6-氨基己酸（ε-Ahx）官能化）生成双官能螯合剂二乙酰基-2-（N ^4-甲基-3-硫代半碳zone）-3- [N ^4-（氨基）-（6-氨基己酸）-3-硫代半碳]]，H ₂ ATSM / A- ε-AHX（1），适用于缀合谷氨酰胺（Gln）的生物活性分子的残基经由TGase。使用物质P（SP）作为模型肽，研究了TGase反应在生物缀合物衍生物合成中的可行性。用氮化nitride-99m标记化合物1和H ₂ ATSM /A-ε-Ahx-SP（2），得到配合物[ ^99m Tc] [Tc（N）（ATSM /A-ε-Ahx）]（^99m Tc1）和[ ^99m Tc] [Tc（N）（ATSM /A-ε-Ahx-SP）]（^99m Tc2）。通过放射性/ UV-RP-HPLC结合ESI-MS分析，分别对添加有载体的产品^{99g / 99m} Tc1确认了^99m Tc1和^99m Tc2的化学同一性和^{99g / 99m} Tc2。研究了在各种环境中孵育后放射性标记复合物的稳定性。将所有结果与从相应的⁶⁴ Cu类似物⁶⁴ Cu1和⁶⁴ Cu2获得的结果进行比较。TGase反应允许1与肽缀合，但是由于螯合剂在所需条件下的不稳定性，其效率不高。SP偶联的复合物在小鼠和人类血清中不稳定。但是，确实可以将BTS系统用作氮化物---99m螯合剂，以高效地进行tech标记，从而使化合物1 值得进一步研究包括单光子发射计算机断层扫描和正电子发射断层扫描成像在内的新型靶向targeted和铜放射性药物。