Salimi Marzieh, Kuddannaya Shreyas, Bulte Jeff W M
Department of Chemical & Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland 21218, United States.
F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Inc., Baltimore, Maryland 21205, United States.
Nano Lett. 2024 Dec 11;24(49):15557-15564. doi: 10.1021/acs.nanolett.4c03553. Epub 2024 Nov 26.
We present a magnetic particle imaging (MPI)-based assay for calculating the blood half-life and tissue uptake of magnetic nanoparticles (MNPs) without the need of labeling them. Dual-catheterized rats received 2.0 mg Fe of Synomag-D70, Synomag-D50, ferucarbotran, and Feraheme by femoral vein injection. The MPI signal of blood samples drawn from the femoral artery at various time points was then measured. Synomag-D70 exhibited biexponential clearance with half-lives of 3.2 and 31.2 min, Synomag-D50 a monoexponential clearance ( = 11.4 min), ferucarbotran a biexponential clearance ( = 2.4 and 10.8 min), and Feraheme a biexponential clearance ( = 60.9 and 4.5 min). MPI of perfused tissues showed MNPs primarily localizing in the spleen, liver, and lymph nodes. Spectrophotometric/chemical iron detection proved unreliable due to residual iron from endogenous blood. The MPI assay is a sensitive and specific method for evaluating the pharmacokinetics of existing MNP formulations and those in the pipeline, with exquisite sensitivity for ultrashort half-lives.
我们提出了一种基于磁粒子成像（MPI）的检测方法，用于计算磁性纳米颗粒（MNP）的血液半衰期和组织摄取，而无需对其进行标记。双导管大鼠通过股静脉注射接受2.0 mg铁的Synomag-D70、Synomag-D50、ferucarbotran和Feraheme。然后测量在各个时间点从股动脉采集的血样的MPI信号。Synomag-D70表现出双指数清除，半衰期分别为3.2分钟和31.2分钟；Synomag-D50表现出单指数清除（ = 11.4分钟）；ferucarbotran表现出双指数清除（ = 2.4分钟和10.8分钟）；Feraheme表现出双指数清除（ = 60.9分钟和4.5分钟）。灌注组织的MPI显示MNP主要定位于脾脏、肝脏和淋巴结。由于内源性血液中的残留铁，分光光度法/化学铁检测被证明不可靠。MPI检测是一种灵敏且特异的方法，可用于评估现有MNP制剂以及研发中的制剂的药代动力学，对超短半衰期具有极高的灵敏度。
