A series of “2 + 1” mixed ligand tricarbonyl complexes of the general formula fac-[Re/^99mTc/¹⁸⁶Re(CO)₃(DDTC)(L)] containing diethyldithiocarbamate (DDTC) as a monoanionic bidentate ligand and a series of monodentate ligands L was synthesized, characterized and evaluated. The impact of ligand L on the radiochemical yield (RCY) and biodistribution of the final compounds was also investigated. DDTC and the appropriate L ligand [cyclohexyl isocyanide (cisc), tert-butyl isocyanide (tbi), triphenylphosphine (PPh₃), methyldiphenylphosphine (PPh₂Me), triphenylarsine (AsPh₃), imidazole (im), and 4-aminopyridine (4AP)] readily reacted in equimolar amounts with the [Et₄N]₂[Re(CO)₃Br₃] precursor to afford fac-[Re(CO)₃(DDTC)(cisc)], Re1, fac-[Re(CO)₃(DDTC)(tbi)], Re2, fac-[Re(CO)₃(DDTC)(PPh₃)], Re3, fac-[Re(CO)₃(DDTC)(PPh₂Me)], Re4, fac-[Re(CO)₃(DDTC)(AsPh₃)], Re5, fac-[Re(CO)₃(DDTC)(im)], Re6 and fac-[Re(CO)₃(DDTC)(4AP)], Re7, complexes in high yields (>80%). All Re complexes were fully characterized by IR, NMR, and in addition Re4, Re5, and Re7 with X-ray crystallography. Analogous reactions as performed with Re were subsequently explored on the ^99mTc and ¹⁸⁶Re-tracer levels using the corresponding fac-[^99mTc/¹⁸⁶Re(CO)₃(H₂O)₃]⁺ precursor. Complexes ^99mTc1 – ^99mTc5, ¹⁸⁶Re1 and ¹⁸⁶Re3 were obtained in high radiochemical yield (>91%), while the complexes ^99mTc6, ^99mTc7 and ¹⁸⁶Re7 formed with radiochemical yields of 55%, 28%, and 75%, respectively. The ^99mTc and ¹⁸⁶Re-complexes were characterized by comparative HPLC analysis using the analogous Re complexes. During histidine and cysteine challenge experiments at 37 °C through 6 h, complexes ^99mTc1 – ^99mTc5 remained > 92% stable, while complexes ^99mTc6 and ^99mTc7 remained only 8% stable through 3 h. Similar studies for ¹⁸⁶Re-complexes showed that ¹⁸⁶Re1 and ¹⁸⁶Re3 remained > 95% stable for up to 48 h, while ¹⁸⁶Re7 had decreased to 7% after 3 h. LogD_7.4 data of ^99mTc1 – ^99mTc5, ¹⁸⁶Re1, and ¹⁸⁶Re3 complexes, which ranged from 2.59 to 3.39, suggested high lipophilicity. Biodistribution studies in healthy Swiss albino mice showed hepatobiliary excretion for ^99mTc1, ^99mTc2, and ^99mTc4, fast blood clearance for ^99mTc4, while high liver uptake and retention for ^99mTc3 and ^99mTc5 were measured. Moreover, ^99mTc2 showed high accumulation in the lungs with sustained retention (52.80% ID/g at 4 h p.i.) and significant brain uptake at 2 min p.i. (1.89% ID/g). The study showed the great influence of monodentate ligand in the synthesis and biodistribution of the mixed ligand complexes.

一系列“2 + 1”混合配体三羰基配合物，通式为fac -[Re/ ^99m Tc/ ¹⁸⁶ Re(CO) ₃ (DDTC)(L)]，含有二乙基二硫代氨基甲酸酯(DDTC)作为单阴离子双齿配体和一系列合成、表征和评估了单齿配体 L。还研究了配体 L 对最终化合物的放射化学产率 (RCY) 和生物分布的影响。DDTC 和合适的 L 配体 [环己基异氰化物 (cisc)、叔丁基异氰化物 (tbi)、三苯膦 (PPh ₃ )、甲基二苯膦 (PPh ₂ Me)、三苯胂 (AsPh ₃)、咪唑 (im) 和 4-氨基吡啶 (4AP)] 容易以等摩尔量与 [Et ₄ N] ₂ [Re(CO) ₃ Br ₃ ] 前体反应得到fac -[Re(CO) ₃ (DDTC )(cisc)], Re1 , fac -[Re(CO) ₃ (DDTC)(tbi)], Re2 , fac -[Re(CO) ₃ (DDTC)(PPh ₃ )], Re3 , fac -[Re( CO) ₃ (DDTC)(PPh ₂ Me)], Re4 , fac -[Re(CO) ₃ (DDTC)(AsPh ₃ )],Re5、fac -[Re(CO) ₃ (DDTC)(im)]、Re6和fac -[Re(CO) ₃ (DDTC)(4AP)]、Re7以高产率 (>80%) 配合。所有 Re 配合物均通过 IR、NMR 以及Re4、Re5和Re7与 X 射线晶体学进行了充分表征。随后使用相应的fac -[ ^99m Tc/ ¹⁸⁶ Re(CO) ₃ (H ₂ O) ₃ ] ^+在99m Tc 和¹⁸⁶ Re-tracer 水平上探索了与 Re 进行的类似反应前体。复合物^99m Tc1 – ^99m Tc5 , ¹⁸⁶ Re1和¹⁸⁶ Re3的放射化学收率高（>91%），而复合物^99m Tc6 , ^99m Tc7和¹⁸⁶ Re7的放射化学收率分别为 55%, 28% 和 75%,分别。^99m Tc 和¹⁸⁶ Re-配合物通过使用类似 Re 配合物的比较 HPLC 分析来表征。在 37 °C 至 6 小时的组氨酸和半胱氨酸挑战实验期间，复合^99m Tc1 – ^99m Tc5保持 > 92% 稳定，而复合物^99m Tc6和^99m Tc7在 3 小时内仅保持 8% 稳定。^对186 Re-complexes的类似研究表明，¹⁸⁶ Re1和¹⁸⁶ Re3在长达 48 小时内保持 > 95% 的稳定性，而¹⁸⁶ Re7在 3 小时后下降到 7%。^99m Tc1 – ^99m Tc5、186 Re1和^{186 Re3}的LogD _7.4数据_复合物的范围从 2.59 到 3.39，表明具有高亲脂性。在健康的瑞士白化病小鼠中进行的生物分布研究表明，^99m Tc1、99m Tc2和^99m Tc4可在肝胆中排泄， ^99m Tc4的血液清除速度快，而^99m Tc3和^99m Tc5的肝脏摄取量和滞留量也^较高。此外，^99m Tc2显示在肺中的高积累并持续滞留（4 小时后 52.80% ID/g）和 2 分钟后显着的脑摄取（1.89% ID/g）。研究表明单齿配体对混合配体配合物的合成和生物分布有很大影响。