Sodium-22-radiolabeled silica nanoparticles as new radiotracer for biomedical applications: in vivo positron emission tomography imaging, biodistribution, and biocompatibility

Abstract

Achraf Al Faraj,1 Basem Alotaibi,2 Abjal Pasha Shaik,3 Khaled Z Shamma,1 Ibrahim Al Jammaz,2 Jürgen Gerl4 1Molecular and Cellular Imaging Lab, Department of Radiological Sciences, College of Applied Medical Sciences, King Saud University, 2Cyclotron and Radiopharmaceutical Department, King Faisal Specialist Hospital and Research Centre, 3Department of Clinical Lab Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 4GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany Abstract: Despite their advantageous chemical properties for nuclear imaging, radioactive sodium-22 (22Na) tracers have been excluded for biomedical applications because of their extremely long lifetime. In the current study, we proposed, for the first time, the use of 22Na radiotracers for pre-clinical applications by efficiently loading with silica nanoparticles (SiNPs) and thus offering a new life for this radiotracer. Crown-ether-conjugated SiNPs (300 nm; -0.18±0.1 mV) were successfully loaded with 22Na with a loading efficacy of 98.1%±1.4%. Noninvasive positron emission tomography imaging revealed a transient accumulation of 22Na-loaded SiNPs in the liver and to a lower extent in the spleen, kidneys, and lung. However, the signal gradually decreased in a time-dependent manner to become not detectable starting from 2 weeks postinjection. These observations were confirmed ex vivo by quantifying 22Na radioactivity using γ-counter and silicon content using inductively coupled plasma-mass spectrometry in the blood and the different organs of interest. Quantification of Si content in the urine and feces revealed that SiNPs accumulated in the organs were cleared from the body within a period of 2 weeks and completely in 1 month. Biocompatibility evaluations performed during the 1-month follow-up study to assess the possibility of synthesized nanocarriers to induce oxidative stress or DNA damage confirmed their safety for pre-clinical applications. 22Na-loaded nanocarriers can thus provide an innovative diagnostic agent allowing ultra-sensitive positron emission tomography imaging. On the other hand, with its long lifetime, onsite generators or cyclotrons will not be required as 22Na can be easily stored in the nuclear medicine department and be used on-demand. Keywords: silica nanoparticles, sodium-22, radiotracer, biodistribution, noninvasive PET imaging, biocompatibility, nanomedicine