Inorganic Chemistry and Centre for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany.
Department of Nuclear Medicine, University Hospital and German Cancer Consortium (DKTK) Partner Site Essen, University of Duisburg-Essen, Essen, Germany.
Acta Biomater. 2020 Jun;109:244-253. doi: 10.1016/j.actbio.2020.03.031. Epub 2020 Apr 4.
Calcium phosphate nanoparticles were covalently surface-functionalized with the ligand DOTA and loaded with the radioisotope Ga. The biodistribution of such Ga-labelled nanoparticles was followed in vivo in mice by positron emission tomography in combination with computer tomography (PET-CT). The biodistribution of Ga-labelled nanoparticles was compared for different application routes: intravenous, intramuscular, intratumoral, and into soft tissue. The particle distribution was measured in vivo by PET-CT after 5 min, 15 min, 30 min, 1 h, 2 h, and 4 h, and ex vivo after 5 h. After intravenous injection (tail vein), the nanoparticles rapidly entered the lungs with later redistribution into liver and spleen. The nanoparticles remained mostly at the injection site following intramuscular, intratumoral, or soft tissue application, with less than 10 percent being mobilized into the blood stream. STATEMENT OF SIGNIFICANCE: The in vivo biodistribution of DOTA-terminated calcium phosphate nanoparticles was followed by PET/CT. To our knowledge, this is the first study of this kind. Four different application routes of clinical relevance were pursued: Intravascular, intramuscular, intratumoral, and into soft tissue. Given the high importance of calcium phosphate as biomaterial and for nanoparticular drug delivery and immunization, this is most important to assess the biofate of calcium phosphate nanoparticles for therapeutic application and also judge biodistribution of nanoscopic calcium phosphate ceramics, including debris from endoprostheses and related implants.
钙磷酸盐纳米粒子通过配体 DOTA 进行共价表面功能化,并负载放射性同位素 Ga。通过正电子发射断层扫描与计算机断层扫描(PET-CT)相结合,在体内小鼠中研究了此类 Ga 标记纳米粒子的生物分布。比较了不同应用途径(静脉内、肌肉内、肿瘤内和软组织内)下 Ga 标记纳米粒子的生物分布。通过 PET-CT 在 5 分钟、15 分钟、30 分钟、1 小时、2 小时和 4 小时后以及 5 小时后进行体内测量粒子分布。静脉内注射(尾静脉)后,纳米粒子迅速进入肺部,随后重新分布到肝脏和脾脏。在肌肉内、肿瘤内或软组织应用后,纳米粒子主要留在注射部位,只有不到 10%被动员到血液中。 意义声明:通过 PET/CT 对 DOTA 端接的钙磷酸盐纳米粒子的体内生物分布进行了跟踪。据我们所知,这是此类研究中的首例。研究了四种具有临床相关性的不同应用途径:血管内、肌肉内、肿瘤内和软组织内。鉴于钙磷酸盐作为生物材料以及纳米药物输送和免疫的重要性,对于治疗应用,评估钙磷酸盐纳米粒子的生物命运非常重要,并且对于纳米级钙磷酸盐陶瓷的生物分布也需要进行判断,包括来自内假体和相关植入物的碎片。
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