Quantitative and correlative biodistribution analysis of 89Zr-labeled mesoporous silica nanoparticles intravenously injected into tumor-bearing mice

Abstract

The biodistribution of ⁸⁹Zr-labeled mesoporous silica nanoparticles (MSNs) was evaluated in detail using a prostate cancer mouse model bearing LNCaP C4-2 and PC-3 tumor xenografts with focus on passive targeting. PEGylation of radiolabeled MSNs significantly improved the blood circulation times and radically enhanced the accumulation in tumors comparable to the accumulation levels previously reported for similar but actively targeted particles. The distribution of the passively targeted MSNs was related to the degree of vascularization of the tumors and did not follow the trends observed in vitro. Correlative analyses of organ-to-blood ratios revealed that little or no accumulation of the particles is observed in the lungs, heart, and brain, and that the particles detected were present in the blood pool. On the other hand, clear accumulation was observed in the liver and spleen, in addition to the uptake in the tumors. The accumulation of particles in the kidney did not correlate with the MSN concentration in the blood, but indicated a rather steady level of particles in the kidney. The results, which partly contradict previous studies, highlight the importance of correlative analyses in order to evaluate the organ accumulation of particles.