With the aim to prepare hypoxia tumor imaging agents, technetium(I) and rhenium(I) tricarbonyl complexes with dipyridylamine (L1 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinylmethyl)-2-pyridinemethanamine; L3 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinyl-methyl)-2-pyridinemethanamine), and iminodiacetate (H₂L2 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxy-methyl)-glycine; H₂L4 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxymethyl)-glycine) ligands appended to sulfonamide or sulfocoumarin carbonic anhydrase inhibitors were synthesized. The Re(I) complexes were characterized using ¹H/¹³C NMR, MS, EA, and in one case the X-ray structure of [Et₃NH][Re(CO)₃(L2)] was obtained. As expected, the Re coordination geometry is distorted octahedral, with a tridentate iminodiacetate ligand in a fac arrangement dictated by the three strong-field CO ligands. Inhibition studies of human carbonic anhydrases (hCAs) showed that the Re sulfocoumarin derivatives were inactive against hCA-I, -II and -IV, but had moderate affinity for hCA-IX. The Re sulfonamides showed improved affinity against all tested hCAs, with [Re(CO)₃(L4)]⁻ being the most active and selective for the hCA-IX isoform. The corresponding ^99mTc complexes were synthesized from fac-[^99mTc(CO)₃(H₂O)₃]⁺, purified by HPLC, and obtained with average 41–76% decay-corrected radiochemical yields and with >99% radiochemical purity. Uptake in HT-29 tumors at 1 h post-injection was highest for [^99mTc(CO)₃(L4)]⁻ (0.14 ± 0.10%ID/g) in comparison to [^99mTc(CO)₃(L1)]⁺ (0.06 ± 0.01%ID/g), [^99mTc(CO)₃(L2)]⁻ (0.03 ± 0.00%ID/g), and [^99mTc(CO)₃(L3)]⁺ (0.07 ± 0.03%ID/g). The uptake in tumors was further reduced at 4 h post-injection. For potential imaging application with single photon emission computed tomography, further optimization is needed to improve the affinity to hCA-IX and uptake in hCA-IX expressing tumors.

为了制备缺氧肿瘤显像剂，tech和二羰基胺与三羰基complex（L1  =  N -{[1-（2,2-dioxido-1,2-benzoxathiin-6-yl）- 1 H -1,2,3-三唑-4-基]甲基} -N-（2-吡啶基甲基）-2-吡啶甲胺; L3  =  N -{[1- [ N-（4-氨基磺酰基苯基）]-1 H -1,2,3-三唑-4-基]甲基} -N-（2-吡啶基-甲基）-2-吡啶甲胺和亚氨基二乙酸酯（H ₂ L2  =  N -{[1-（2,2-dioxido -1,2-苯并氧杂i啶-6-基）-1 H -1,2,3-三唑-4-基]甲基} -N-（羧甲基）-甘氨酸; H₂ L4  = 附在磺酰胺上的N -{[1- [ N-（4-氨基磺酰基苯基）]-1 H -1,2,3-三唑-4-基]甲基} -N-（羧甲基）-甘氨酸）配体合成了香豆素碳酸酐酶抑制剂。使用¹ H / ¹³ C NMR，MS，EA对Re（I）配合物进行表征，在一种情况下，获得[Et ₃ NH] [Re（CO）₃（L2）]的X射线结构。如所预期的，重新协调的几何形状扭曲的八面体，具有在三齿配体亚氨基二乙酸FAC排列由三个强场CO配体决定。对人类碳酸酐酶（hCAs）的抑制研究表明，Re磺香豆素衍生物对hCA-I，-II和-IV无活性，但对hCA-IX具有中等亲和力。Re磺酰胺类药物对所有测试的hCA均显示出更高的亲和力，其中[Re（CO）₃（L4）] ^-对hCA-IX同工型最具活性和选择性。由fac- [ ^99m Tc（CO）₃（H ₂ O）₃ ] ⁺合成相应的^99m Tc络合物，经HPLC纯化，获得平均41-76％衰减校正后的放射化学收率和> 99％的放射化学纯度。[ ^99m Tc（CO）₃（L4）] ^-（0.14±0.10％ID / g）与[ ^99m Tc（CO）₃（L1）]相比，注射后1 h HT-29肿瘤的摄取最高。⁺（0.06±0.01％ID / g），[ ^99m Tc（CO）₃（L2）] ^-（0.03±0.00％ID / g）和[ ^99m Tc（CO）₃（L3）] ⁺（0.07±0.03％ID / g）。注射后4小时，肿瘤的摄取进一步降低。对于具有单光子发射计算机断层摄影技术的潜在成像应用，需要进一步优化以提高与hCA-IX的亲和力以及表达hCA-IX的肿瘤的摄取。