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11.
Re(I) and Tc(I) Complexes for Targeting Nitric Oxide Synthase: Influence of the Chelator in the Affinity for the Enzyme
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Bruno L. Oliveira Maurício Morais Filipa Mendes Irina S. Moreira Carlos Cordeiro Pedro A. Fernandes Maria J. Ramos Roger Alberto Isabel Santos João D. G. Correia 《Chemical biology & drug design》2015,86(5):1072-1086
Aiming to design 99mTc complexes for probing nitric oxide synthase (NOS) by SPECT, we synthesized conjugates ( L4 – L6 ) comprising a NOS‐recognizing moiety connected to a diamino‐propionic acid (dap) chelating unit. The conjugates led to complexes of the type fac‐[M(CO)3(?3‐L)] (M = Re/99mTc; Re4 / Tc4 : L = L4 ; Re5 / Tc5 : L = L5 ; Re6 / Tc6 : L = L6 ). Enzymatic studies showed that L4 and L5 , but not L6 , gave complexes ( Re4 and Re5 ) that are less potent than the conjugates. To rationalize these results, we performed docking and molecular dynamics simulations. The high affinity of L4 and L5 is due to the strong interactions between the dap chelator and polar residues of the binding cavity. These interactions are hampered by metallation resulting in complexes with lower affinity. The higher potency of Re5 compared to Re4 was assigned to the increased bulkiness of Re5 and the presence of additional anchoring groups that better fit the active site and provide more extensive contacts. In turn, Re6 is too bulky and its organometallic tail is oriented toward the peripheral pocket of iNOS, leading to loss of contacts and a lower affinity. These results were compared with our previous results obtained with analogue complexes stabilized by a pyrazolyl‐diamine chelating unit. 相似文献
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Gregorio Fantini Elena Dallerba Massimiliano Massi Andrew B. Lowe 《Macromolecular chemistry and physics.》2020,221(15)
The synthesis and photophysical properties of well‐defined polymer‐rhenium(I) hybrid materials is described. Reversible addition‐fragmentation chain transfer polymerization of pentafluorophenyl acrylate yields a parent homopolymer that serves as a reactive scaffold for the preparation of a series of new statistical copolymers containing pendent pyridyl functional groups in conjunction with various other repeat unit species. Attachment of [Re(CO)3(phen)]+ fragments via coordination through the pendent pyridyl groups yields the hybrid metal‐copolymer materials. Photophysical studies confirm successful rhenium coordination as judged from the absorption and emission profiles of the hybrid materials and further verify that the polymeric scaffold has no discernable effect on the luminescent properties of the coordinated rhenium species. 相似文献
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目的:探讨188铼(188Re)血管内照射对血管平滑肌细胞增殖和凋亡的影响.方法:40只新西兰白兔随机分为对照组(n=20只)和照射组(n=20只),均行腹主动脉球囊内皮拉伤术.照射组内皮拉伤后行188Re血管内照射治疗,管腔下0.5 mm处累计吸收剂量为15 Gy;对照组则不行血管内照射.分别于术后1、3周处死动物,取病理组织学标本进行增殖细胞核抗原(PCNA)和凋亡细胞分析.结果:照射组第1、3周PCNA细胞阳性率分别为(27.69±7.04)%与(20.88±4.55)%,明显低于对照组(42.71±6.11)%、(29.48±10.13)%(P均<0.05);照射组第3周平滑肌细胞凋亡细胞百分比为(40.16±7.93)%,明显高于对照组(28.50±9.39)%(P=0.018).结论:188Re血管内照射能抑制血管平滑肌细胞增殖,促进血管平滑肌细胞凋亡,从而抑制新生内膜增生,减少PTCA术后再狭窄的发生. 相似文献
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目的:研究乳腺癌细胞(MCF-7)对188Re标记二乙三胺五乙酸葡糖胺(DTPA-DG)的摄取。方法:采用γ计数法在不同时间段评价乳腺癌细胞(MCF-7)对188Re-DTPA-DG(3.7kBq/10μl)的摄取。结果:乳腺癌肿瘤细胞(MCF-7)对188Re-DTPA-DG的摄取率明显高于对照组188ReO4-(P<0.05);实验组30min与4h细胞摄取率差异存在显著性意义(P<0.05),而对照组不同时间点细胞摄取率差异无显著性意义(P>0.05)。结论:188Re-DTPA-DG容易被乳腺癌细胞(MCF-7)摄取,使188Re在肿瘤细胞内发挥辐射效应成为可能,从而为临床肿瘤治疗提供理论依据。 相似文献
16.
姜黄素固体分散体的制备及体外溶出特性 总被引:2,自引:0,他引:2
目的制备姜黄素固体分散体,改善姜黄素的溶出度。方法以泊洛沙姆188为载体,用溶剂熔融法制备固体分散体,以差示扫描量热法、X射线粉末衍射进行物相鉴定,并对所得样品进行体外溶出度研究。结果姜黄素固体分散体中药物部分以分子状态分散,部分以微晶分散.药物的累积溶出速率随载体比例增加而增加,以1:9的比例效果最好。结论采用泊洛沙姆188制备的固体分散体能显著提高姜黄素的体外溶出度。 相似文献
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目的 制备放射免疫导向药物用以诊断和治疗膀胱癌。 方法 通过 2 巯基直接还原标记法将放射性核素188Re(188铼 )标记抗人膀胱癌单克隆抗体BDI 1,标记产物188Re BDI 1经尾静脉注入荷人膀胱癌裸鼠体内 ,检测其在裸鼠体内的放射性分布。 结果 188Re BDI 1的标记率为30 % ,放射化学纯度为 90 % ,免疫活性分数为 5 8.6 8%。在裸鼠体内 ,肿瘤对188Re BDI 1的摄取率在2 3h达到高峰 ,以后随时间推移 ,逐步下降。 2 3h时T/NT比值 (肿瘤与正常组织的放射性计数之比 )明显增加 ,平均T/NT为 4.42 ,最大为 16 .19(肿瘤 /肌肉 ) ,随时间推移T/NT比值有所下降 ,48h时T/NT比值仍保持在高水平 10 .41(肿瘤 /肌肉 )、70h时T/NT比值 3.41(肿瘤 /肌肉 )。结论 188Re BDI 1在裸鼠体内对膀胱癌移植瘤有靶向定位作用。188Re BDI 1有可能成为膀胱癌放射免疫显像和治疗的导向药物。 相似文献
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Miao Y Owen NK Whitener D Gallazzi F Hoffman TJ Quinn TP 《International journal of cancer. Journal international du cancer》2002,101(5):480-487
The purpose of our study was to optimize melanoma tumor uptake of 188Re-CCMSH and reduce its nonspecific kidney retention. Nephrotoxicity is often a serious problem associated with targeted radiotherapy, therefore, increasing the tumor/kidney uptake ratio of 188Re-CCMSH is crucial for optimizing its therapeutic efficacy. Structural modification of the peptide and amino acid co-infusion were investigated as strategies to improve the tumor/kidney uptake ratio of 188Re-CCMSH. The substitution of Lys11 with Arg11 was examined to determine if removal of lysine from the peptide would improve kidney clearance without sacrificing tumor uptake. The pharmacokinetics of 188Re-CCMSH and 188Re-(Arg(11))CCMSH were determined in B16/F1 murine melanoma-bearing C57 mice. Tumor uptake values of (188)Re-CCMSH and 188Re-(Arg(11))CCMSH were 15.03 +/- 5.20% ID/g and 20.44 +/- 1.91% ID/g at 1 hr postinjection and 1.94 +/- 0.47% ID/g and 3.50 +/- 2.32% ID/g at 24 hr postinjection. Renal retention of 188Re-(Arg(11))CCMSH was 11.79 +/- 1.29 ID/g and 3.67 +/- 0.51 ID/g at 1 hr and 4 hr postinjection, which was a greater than 50% reduction compared to 188Re-CCMSH. The Arg for Lys substitution in 188Re-(Arg(11))CCMSH resulted in improved tumor uptake and reduced kidney retention. Renal retention of both 188Re-CCMSH and 188Re-(Arg(11))CCMSH were significantly reduced by co-injection of 20 mg of L-lysine, L-arginine and a combination of L-lysine:L-arginine. Tumor/kidney uptake values for 188Re-CCMSH and 188Re-(Arg(11))CCMSH were maximally reduced by 52.9% and 46.3%, respectively. However, even with amino acid co-injection, the tumor/kidney ratio of 188Re-CCMSH was lower than that of 188Re-(Arg(11))CCMSH. Improved tumor uptake and reduced kidney retention of 188Re-(Arg(11))CCMSH will facilitate targeted irradiation of melanoma tumors while minimizing the dose to the kidneys. 相似文献
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目的:估算188Re-DTPA-DG(二乙三胺五乙酸-脱氧葡萄糖)肿瘤治疗中肿瘤和主要器官内照射吸收剂量.方法:荷MCF-7乳腺癌裸鼠尾静脉注射后,在3、12、24h处死动物,测定小鼠体内各脏器放射性分布,换算至标准人体内分布数据,按MIRD法计算188Re-DTPA-DG全身、肿瘤和各主要器官的平均总吸收剂量.结果:肿瘤辐射剂量为255.32mSv/MBq,其他脏器内照射吸收剂量在0.002~6.850 mGy/MBq之间,有效剂量为1.420±0.043 mSv/MBq.结论:188Re-DTPA-DG可以作为临床上肿瘤治疗和诊断药物的可能. 相似文献
20.
目的 探讨^188Re—HEDP(^188铼-1-羟基亚乙基二瞵酸盐)治疗转移性骨肿瘤疼痛的临床价值。方法 用^188W-^188Re发生器淋洗的^188Re示踪剂制备^188Re—HEDP,38例癌骨转移患者用^188Re—HEDP治疗,观察其疗效。结果 38例经^188Re—HEDP治疗后骨痛消失12例(31.6%),骨痛明显减轻19例(50%),止痛总有效率为83.7%;治疗后骨转移灶完全消失1例(2.6%),转移灶减少或缩小在50%以上3例(7.9%),减少或缩小在25%以上5例(13.2%),转移灶消失或缩小的总有效率为23.7%。结论 ^188Re—HEDP对恶性肿瘤多发性骨转移所致疼痛有明显疗效,且安全无副作用。 相似文献