Room: Track 3
Purpose: Gold nanoparticles (GNPs) are attractive theranostic agents for tumor therapy and molecular imaging. In this study, we developed an x-ray fluorescence computed tomography (XFCT) system onboard a murine stereotactic radiotherapy system to noninvasively monitor the biodistribution of GNPs. We also designed PSMA-targeted GNPs to improve GNP accumulation and retention time in prostate tumors.
Methods: 15-nm GNPs were functionalized with polyethylene glycol (PEG) to keep GNPs from aggregating and to avoid uptake by the reticular endothelial system. PEGylated GNPs were conjugated to anti-PSMA antibodies using 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxy sulfosuccinimide. GNP quantification imaging was accomplished on an in-house-developed dual-modality XFCT/transmission CT imaging and radiotherapy system which is composed of: a benchtop x-ray tube, a translation/rotation stage, a flat panel detector for transmission projection detection, a 3D printed source collimator, and a silicon drift detector to collect L-shell x-ray fluorescence. Mice (n=6) bearing LNCaP xenografts were injected with GNP intravenously to evaluate active targeting efficiency. In vivo GNP pharmacokinetic analysis was completed using x-ray fluorescence signals, and 3D tumor XFCT was conducted 24hrs post GNP injection. The tumor was dissected post-imaging for inductively coupled plasma mass spectrometry (ICP-MS).
Results: In vivo GNP x-ray fluorescence signals demonstrated the higher accumulation and longer retention of PSMA-targeted GNPs compared to non-targeted GNPs. Active-targeting GNPs reached their peak accumulation in tumor at ~24hrs after intravenous injection. XFCT simultaneously identified GNP spatial distribution and quantified GNP concentration. Both tumor in vivo and ex vivo XFCT shows ~3 times higher accumulation of PSMA-targeted GNPs. Moreover, ICP-MS results validated the accuracy of XFCT imaging in GNP quantification.
Conclusion: PSMA-targeted GNPs increase XFCT tumor detection sensitivity, which is especially beneficial to visualize heterogeneous distribution of GNPs in prostate tumors. XFCT onboard the murine stereotactic radiotherapy system will be a helpful tool to further investigate the GNP-aided radiotherapy.