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<p>In this work, a <sup>99m</sup>Tc-labeled polyethylene glycol chain-modified bis(4-methyl-2-nitroimidazole) propylene amine oxime (PnAO) complex, oxo[[15, 15, 21, 21-tetramethyl-1, 35-bis(4-methyl-2-nitro-1<i>H</i>-imidazol-1-yl)-3, 6, 9, 12, 24, 27, 30, 33-octaoxa-16, 20-diazapentatri-acontane-14, 22-dione dioximato] (3-)-<i>N</i>, <i>N′</i>, <i>N′′</i>, <i>N′′′</i>]-technetium-99m ([<sup>99m</sup>Tc]Tc-Me2P2O4) was prepared. The radiochemical purity of [<sup>99m</sup>Tc]Tc-Me2P2O4 was greater than 95% with good stability, and its logD<sub>7.4</sub> was 0.98 ± 0.01. In the study of cellular uptake in chronic hypoxia and normoxia (S180, HeLa, HT-29 cell lines), [<sup>99m</sup>Tc]Tc-Me2P2O4 showed obvious hypoxic cellular selectivity, with chronic hypoxic/ normoxic cellular uptake ratios of 4.24 ± 0.09 (S180), 1.47 ± 0.02 (HeLa) and 2.79 ± 0.04 (HT-29) at 240&#xa0;min. And the acute hypoxic/normoxic cellular uptake ratio of [<sup>99m</sup>Tc]Tc-Me2P2O4 in S180 cell line was 2.68 ± 0.01 at 240&#xa0;min. It can be seen that S180 chronic hypoxia cellular experiment have more advantages in evaluating a hypoxia imaging agent. The results of biodistribution experiments and SPECT-CT imaging of S180 tumor-bearing mice confirmed that [<sup>99m</sup>Tc]Tc-Me2P2O4 was retained in the tumor (0.25 ± 0.08%ID/g, 8&#xa0;h). In addition, the results of HIF-1α immunohistochemical staining and autoradiography showed that [<sup>99m</sup>Tc]Tc-Me2P2O4 targeted the hypoxic regions of ​​the tumor. Consequently, [<sup>99m</sup>Tc]Tc-Me2P2O4 may serve as a viable candidate for hypoxia imaging.</p>

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Preparation and biological evaluation of 99mTc-labeled polyethylene glycol-modified bis(4-methyl-2-nitroimidazole) PnAO as a hypoxia imaging agent

  • 期刊论文

  • 发表日期：

    2025年4月5日

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  • Shuo Li,
  • Taiwei Chu

摘要

In this work, a 99mTc-labeled polyethylene glycol chain-modified bis(4-methyl-2-nitroimidazole) propylene amine oxime (PnAO) complex, oxo[[15, 15, 21, 21-tetramethyl-1, 35-bis(4-methyl-2-nitro-1H-imidazol-1-yl)-3, 6, 9, 12, 24, 27, 30, 33-octaoxa-16, 20-diazapentatri-acontane-14, 22-dione dioximato] (3-)-N, N′, N′′, N′′′]-technetium-99m ([99mTc]Tc-Me2P2O4) was prepared. The radiochemical purity of [99mTc]Tc-Me2P2O4 was greater than 95% with good stability, and its logD7.4 was 0.98 ± 0.01. In the study of cellular uptake in chronic hypoxia and normoxia (S180, HeLa, HT-29 cell lines), [99mTc]Tc-Me2P2O4 showed obvious hypoxic cellular selectivity, with chronic hypoxic/ normoxic cellular uptake ratios of 4.24 ± 0.09 (S180), 1.47 ± 0.02 (HeLa) and 2.79 ± 0.04 (HT-29) at 240 min. And the acute hypoxic/normoxic cellular uptake ratio of [99mTc]Tc-Me2P2O4 in S180 cell line was 2.68 ± 0.01 at 240 min. It can be seen that S180 chronic hypoxia cellular experiment have more advantages in evaluating a hypoxia imaging agent. The results of biodistribution experiments and SPECT-CT imaging of S180 tumor-bearing mice confirmed that [99mTc]Tc-Me2P2O4 was retained in the tumor (0.25 ± 0.08%ID/g, 8 h). In addition, the results of HIF-1α immunohistochemical staining and autoradiography showed that [99mTc]Tc-Me2P2O4 targeted the hypoxic regions of ​​the tumor. Consequently, [99mTc]Tc-Me2P2O4 may serve as a viable candidate for hypoxia imaging.