给药途径对Re-188标记白蛋白微球生物分布的影响

V. Tishchenko, V. Petriev, O. Vlasova, E. Stepchenkova
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摘要

目前,放射性标记微球已成为原发性和转移性肝癌放射栓塞治疗的常用工具。人血清白蛋白微球(HSA)是一种独特的载体,用于选择性和控制放射性核素递送到恶性肿瘤。铼-188 (Re-188)以β粒子(2.12 MeV(71.1%)和1.965 MeV(25.6%)和γ辐射(155 keV(15.1%))衰变,是目前最有效和最有前途的癌症治疗放射性核素之一。本研究旨在研究Re-188标记的人血清白蛋白微球(Re-188- hsa)在不同给药途径下在动物体内的生物分布。95%以上的微球粒径在10 ~ 20 μm之间。本研究对移植Lewis腺癌的远交种小鼠和近交种C57BL/6小鼠进行静脉、肌肉和肿瘤内给药。经静脉注射后,Re-188-HSA在各脏器组织中含量最高:肺最高达311.3%/g,甲状腺最高达74.30%/g,肝脏最高达12.70%/g,血液最高达0.81% /g。肌肉注射188Re-HSA后,除甲状腺(1,10-17.80%/g)外,各脏器组织中188Re-HSA浓度均显著降低,均不超过1%/g。经瘤内注射后,Re-188-HSA在肿瘤中的含量为16.7 ~ 26.8%/g,高于其他脏器组织。因此,Re-188-HSA的给药途径显著影响其在体内的行为。所得结果可用于评价Re-188-HSA在血管内或肿瘤内给药后用于放射性核素肿瘤治疗的潜力。
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Effect of administration route on the biodistribution of albumin microspheres labelled with Re-188
Nowadays the radiolabeled microspheres are established tools for radioembolization of primary and metastatic liver cancer. Human serum albumin microspheres (HSA) are unique carriers for selective and controlled radionuclide delivery to malignant tumors. Rhenium-188 (Re-188), which decays with beta particles (2.12 MeV (71.1%) and 1.965 MeV (25.6%) and gamma emission (155 keV (15.1%)) is one of the most available and promising generator-based radionuclide for cancer therapy. The purpose of this work was to study the biodistribution of microspheres based on hu-man serum albumin labeled with Re-188 (Re-188-HSA) in animals after different routes of admin-istration. The size of more than 95% of microspheres was 10-20 μm. The studies were carried out on outbred white mice and inbred C57BL/6 mice with transplanted Lewis adenocarcinoma after intravenous, intramuscular and intratumoral administration. After intravenous injection the high-est amount of Re-188-HSA in organs and tissues was observed: up to 311.3%/g in lungs, up to 74.30%/g in thyroid gland, up to 12.70%/g in liver, up to 0,81%/g in blood. After the intramuscular injection of 188Re-HSA, the concentration of 188Re-HSA in organs and tissues was significantly lower and did not exceed 1%/g, except for thyroid gland (1,10-17.80%/g). After intratumoral injec-tion the amount of Re-188-HSA in tumor varied from 16.7 to 26.8%/g, that was higher as compared with other organs and tissues. Thus, the routes of Re-188-HSA administration significantly affect its behavior in the body. The obtained results can be used to evaluate the Re-188-HSA potential for radionuclide tumor therapy after intravascular or intratumoral administration.
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