Ghai Aanchal, Singh Baljinder, Panwar Hazari Puja, Schultz Michael K, Parmar Ambika, Kumar Pardeep, Sharma Sarika, Dhawan Devinder, Kumar Mishra Anil
Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India.
Department of Nuclear Medicine & PET, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, India.
Appl Radiat Isot. 2015 Nov;105:40-46. doi: 10.1016/j.apradiso.2015.07.021. Epub 2015 Jul 22.
The present study describes the optimization of (68)Ga radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0min and reaction temperature ranging between 90 and 100°C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([(68)Ga]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with αVβ3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the (68)Ga labeled product for imaging and treating angiogenesis respectively.
本研究描述了用聚酰胺 - 胺(PAMAM)树枝状大分子 - DOTA共轭物对(68)Ga进行放射性标记的优化过程。共轭物(PAMAM - DOTA)浓度为11.69µM时,在pH 4.0、孵育时间30.0分钟以及反应温度在90至100°C之间的条件下,提供了超过93.0%的最佳放射性标记效率。发现经衰变校正后的放射化学产率为79.4±0.01%。放射性标记制剂([(68)Ga]-DOTA - PAMAM - D)在室温下和血清中长达4小时保持稳定(放射性标记效率为96.0%)。观察到血浆蛋白结合率为21.0%。静脉注射后,30分钟内50.0%的示踪剂从血液循环中清除,1.0小时后血液中残留的注射活性小于1.0%。动物体内生物分布研究表明,示踪剂通过肾脏排泄,注射后1小时约0.33%的注射剂量每克组织积聚在肿瘤中。动物PET成像支持了动物器官的生物分布数据,显示肿瘤中示踪剂有良好的“非特异性”摄取,且排泄主要通过肾脏。此外,将DOTA - PAMAM - D与αVβ3受体靶向肽共轭以及在树枝状大分子上加载药物,可能分别提高(68)Ga标记产物用于成像和治疗血管生成的特异性。
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