Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400, Montevideo, Uruguay.
Laboratorio de ATN en Bioquímica y Biotecnología, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400, Montevideo, Uruguay.
AAPS PharmSciTech. 2021 Mar 24;22(3):115. doi: 10.1208/s12249-021-01984-1.
Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on Tc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with Tc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of Tc-HYNIC liposome and Tc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that Tc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.
纳米医学是一门需求量很大的学科。由于脂质体具有物理化学性质，使其能够作为药物和放射性同位素的纳米载体，因此受到了越来越多的关注，这些放射性同位素可用于诊断和治疗癌症。为了获得基于 Tc 标记脂质体的新型通透性癌症成像剂，我们描述了微波辅助合成硬脂酰 6-（亚苄基腙基）烟酰胺脂质，该脂质被包含在两种制剂中：纳米尺寸的肼基烟酸（HYNIC）脂质体及其聚乙二醇化的涂层类似物 HYNIC-PEG 脂质体。通过硬脂酰 6-（亚苄基腙基）烟酰胺对 Tc 的放射性标记被发现是容易、可重复且稳定的，两种脂质体制剂的放射化学纯度均高达 94±1.7%。在正常和黑色素瘤荷瘤 C57BL/6 小鼠中进行了 4 h 和 24 h 的生物分布研究和 4 h 的闪烁成像。4 h 的生物分布研究显示 Tc-HYNIC 脂质体和 Tc-HYNIC-PEG 脂质体的肿瘤摄取率分别为 1.1±0.6 和 2.5±0.4，24 h 后摄取率分别为 1.8±0.5 和 3.0±1.1。闪烁成像显示两种脂质体制剂在黑色素瘤荷瘤小鼠中均能明显摄取肿瘤。我们的结果表明，Tc 硬脂酰 6-（亚苄基腙基）烟酰胺脂质体可用作诊断性非侵入性体内肿瘤靶向剂，能够评估肿瘤通透性和发展，可用于个体化化疗计划。
