Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China.
Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China.
Int J Nanomedicine. 2023 Aug 2;18:4431-4444. doi: 10.2147/IJN.S416741. eCollection 2023.
BSA-biomineralized Gd nanoparticles (Gd@BSA NPs) have been recognized as promising nanoscale MR contrast agents. The aim of this study was to carry out a preclinical evaluation of these NPs in a middle-sized animal model (rabbits).
New Zealand white rabbits were treated intravenously with Gd@BSA NPs (0.02 mmol Gd/kg) via a clinically-used high-pressure injector, with commercial Gd-diethylene triamine pentaacetate (Gd-DTPA)-injected group as control. Then MR angiography was performed according to the standard clinical protocol with a 3.0-T MR scanner. The SNR and CNR of the main arteries and branches were monitored. Pharmacokinetics and bioclearance were continuously evaluated in blood, urine, and feces. Gd deposition in vital organs was measured by ICP‒MS. Weight monitoring, HE staining, and blood biochemical analysis were also performed to comprehensively estimate systemic toxicity.
The ultrasmall Gd@BSA NPs (<6 nm) exhibited high stability and T1 relaxivity. Compared to Gd-DTPA, Gd@BSA NPs demonstrated superior vascular system imaging performance at ultralow doses, especially of the cardiac artery and other main branches, and exhibited a significantly higher SNR and CNR. Notably, the Gd@BSA NPs showed a shorter half-life in blood, less retention in organs, and improved biocompatibility.
The preclinical evaluations here demonstrated that Gd@BSA NPs are promising and advantageous MR CA candidates that can be used at a low dose with excellent MR imaging performance, thus suggesting its further clinical trials and applications.
BSA 生物矿化钆纳米颗粒（Gd@BSA NPs）已被认为是很有前途的纳米级磁共振对比剂。本研究旨在对中型动物模型（兔）进行这些 NPs 的临床前评估。
新西兰白兔通过临床使用的高压注射器静脉内给予 Gd@BSA NPs（0.02 mmol Gd/kg），以 Gd-二乙烯三胺五乙酸（Gd-DTPA）注射组作为对照。然后，根据标准临床方案使用 3.0-T MR 扫描仪进行磁共振血管造影。监测主要动脉和分支的 SNR 和 CNR。通过 ICP-MS 连续评估血液、尿液和粪便中的药代动力学和生物清除率。通过 ICP-MS 测量重要器官中的 Gd 沉积。还进行了体重监测、HE 染色和血液生化分析，以全面评估全身毒性。
超小 Gd@BSA NPs（<6nm）表现出高稳定性和 T1 弛豫率。与 Gd-DTPA 相比，Gd@BSA NPs 在超低剂量下表现出优异的血管系统成像性能，尤其是在心脏动脉和其他主要分支，表现出更高的 SNR 和 CNR。值得注意的是，Gd@BSA NPs 在血液中的半衰期更短，在器官中的滞留量更少，生物相容性更好。
这里的临床前评估表明，Gd@BSA NPs 是很有前途和有利的磁共振对比剂候选物，可在低剂量下使用，具有优异的磁共振成像性能，因此建议进行进一步的临床试验和应用。
