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(68)Ga标记的DOTA-聚酰胺-胺树枝状大分子共轭物的放射性标记优化与表征——动物体内生物分布及PET成像结果

Radiolabeling optimization and characterization of (68)Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results.

作者信息

Ghai Aanchal, Singh Baljinder, Panwar Hazari Puja, Schultz Michael K, Parmar Ambika, Kumar Pardeep, Sharma Sarika, Dhawan Devinder, Kumar Mishra Anil

机构信息

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.

出版信息

Appl Radiat Isot. 2015 Nov;105:40-46. doi: 10.1016/j.apradiso.2015.07.021. Epub 2015 Jul 22.


DOI:10.1016/j.apradiso.2015.07.021
PMID:26232562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5538890/
Abstract

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.

摘要

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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本文引用的文献

[1]
Labeling polyamidoamine (PAMAM) dendrimers with technetium-99m via hydrazinonicotinamide (HYNIC).

Curr Radiopharm. 2014

[2]
Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates labeled with 177Lu: radiolabeling and biodistribution studies.

Appl Radiat Isot. 2014-2

[3]
A new automated NaCl based robust method for routine production of gallium-68 labeled peptides.

Appl Radiat Isot. 2013-6

[4]
Maturation of a key resource - the germanium-68/gallium-68 generator: development and new insights.

Curr Radiopharm. 2012-7

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Curr Radiopharm. 2012-4

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Radiolabeling of PAMAM dendrimers conjugated to a pyridine-N-oxide DOTA analog with ¹¹¹In: Optimization of reaction conditions and biodistribution.

J Pharm Biomed Anal. 2011-6-22

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Biomacromolecules. 2010-12-3

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Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.

Bioorg Med Chem. 2010-7-8

[9]
PAMAM dendrimers as solubilizers and hosts for 8-methoxypsoralene enabling transdermal diffusion of the guest.

Int J Pharm. 2010-7-22

[10]
Macromolecular and dendrimer-based magnetic resonance contrast agents.

Acta Radiol. 2010-9

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