Pharmacokinetics and biodistribution studies of [99mTc]-Labeled ZIF-8 nanoparticles to pave the way for image-guided drug delivery and theranostics

Abstract

The last few years have witnessed an increasing interest in using metal-organic frameworks (MOFs), a newly emerging class of highly porous nanomaterials. Countless studies have been performed on the synthesis, characterization, and applications of these nanomaterials. However, tracking these nanoparticles' in vivo fate is of great importance for practical applications. Herein, we conducted a profound investigation of the pharmacokinetics and biodistribution of MOF nanoparticles. To this end, Zn-based MOF (i.e., ZIF-8 nanoparticles) were synthesized and radiolabeled with technetium-99 m [99mTc] radioisotope with high labeling efficiency. The prepared nanoparticles exhibited high in-vitro stability. The biodistribution and pharmacokinetic studies were performed in animals, and the data were compared with free [99mTc]. The biodistribution was investigated using the single-photon emission computed tomography (SPECT) imaging technique. The highest ZIF-8 NPs accumulation was observed in the lung, while free [99mTc] was mainly accumulated in the animal's stomach. The results revealed that the half-life of [99mTc]-ZIF-8 nanoparticles in the blood was almost twice that of sodium pertechnetate. Accordingly, due to their high pulmonary biodistribution, ZIF-8 NPs can considerably improve the pharmacokinetics of encapsulated agents and be used for lung targeting. This study paves the way for developing favorable nanocarriers for diagnostic, therapeutic, and theranostic applications.