Ogawa Kazuma, Nishizawa Kota, Washiyama Kohshin, Munekane Masayuki, Fuchigami Takeshi, Echigo Hiroaki, Mishiro Kenji, Hirata Saki, Wakabayashi Hiroshi, Takahashi Kazuhiro, Kinuya Seigo
Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Nucl Med Biol. 2023 Jul-Aug;122-123:108369. doi: 10.1016/j.nucmedbio.2023.108369. Epub 2023 Jul 22.
As sigma receptors are abundantly expressed on different types of cancer cells, several radiolabeled sigma receptor ligands have been developed for cancer imaging and therapy. Previously, we synthesized and evaluated radioiodinated aza-vesamicol derivatives, [I]pICNV, [I]mICN5V, and [I]mICN5V. They accumulated in tumors, and [I]mICN5V and [I]mICN5V showed higher tumor to non-target tissue ratios than [I]pICNV. Therefore, we synthesized and evaluated the corresponding At-labeled compounds, [At]mAtCN5V and [At]mAtCN5V, for targeted alpha therapy (TAT).
[At]mAtCN5V and [At]mAtCN5V were prepared by the standard method of electrophilic astatodestannylation of the corresponding trimethylstannyl precursors. Cellular uptake experiments, and biodistribution experiments and therapeutic experiments in tumor-bearing mice were performed.
The radiochemical yields of [At]mAtCN5V and [At]mAtCN5V were 45.5 ± 14.4% and 56.9 ± 13.8%, respectively. After HPLC purification, their radiochemical purities were over 95%. [At]mAtCN5V and [At]mAtCN5V showed high uptake in DU-145 cells. They demonstrated high accumulation in tumors (6.9 ± 1.4%injected dose/g and 5.1 ± 1.4%injected dose/g at 1 h, respectively) and similar biodistribution tendencies compared with the corresponding I-labeled compounds. A single injection of [At]mAtCN5V (0.48 MBq) or [At]mAtCN5V (0.48 MBq) significantly inhibited tumor growth.
These results indicated that [At]mAtCN5V and [At]mAtCN5V could be potential candidates for TAT.
由于σ受体在不同类型的癌细胞上大量表达，已开发出几种放射性标记的σ受体配体用于癌症成像和治疗。此前，我们合成并评估了放射性碘化氮杂维甲酰胆碱衍生物[I]pICNV、[I]mICN5V和[I]mICN5V。它们在肿瘤中蓄积，并且[I]mICN5V和[I]mICN5V的肿瘤与非靶组织比率高于[I]pICNV。因此，我们合成并评估了相应的砹标记化合物[At]mAtCN5V和[At]mAtCN5V用于靶向α治疗（TAT）。
[At]mAtCN5V和[At]mAtCN5V通过相应三甲基锡前体的亲电砹代脱锡标准方法制备。进行了细胞摄取实验、生物分布实验以及在荷瘤小鼠中的治疗实验。
[At]mAtCN5V和[At]mAtCN5V的放射化学产率分别为45.5±14.4%和56.9±13.8%。经高效液相色谱纯化后，它们的放射化学纯度超过95%。[At]mAtCN5V和[At]mAtCN5V在DU - 145细胞中显示出高摄取。它们在肿瘤中显示出高蓄积（分别在1小时时为6.9±1.4%注射剂量/克和5.1±1.4%注射剂量/克），并且与相应的碘标记化合物相比具有相似的生物分布趋势。单次注射[At]mAtCN5V（0.48 MBq）或[At]mAtCN5V（0.48 MBq）可显著抑制肿瘤生长。
这些结果表明[At]mAtCN5V和[At]mAtCN5V可能是TAT的潜在候选物。
