@article{Lee_Kim_Kim_Kwon_Bang_Lee_Song_Hahm_Shim_Han_et al._2011, title={Pharmacokinetics and Biodistribution of Human Serum Albumin-TIMP-2 Fusion Protein Using Near-Infrared Optical Imaging}, volume={14}, url={https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/10533}, DOI={10.18433/J3H88D}, abstractNote={Purpose TIMP-2 has been studied as an attractive cancer therapeutic candidate, and a TIMP-2 fusion protein (HSA/TIMP-2) displayed effective anticancer activity, despite a lack of information about its pharmacokinetics (PK) and biodistribution. The purpose of this work was to assess the PK and biodistribution of HSA/TIMP-2 as well as to quantify accumulated HSA/TIMP-2 in tumors. Methods Cy5.5 near-infrared (NIR) fluorescence was conjugated to the HSA/TIMP-2 protein (Cy5.5–HSA/TIMP-2) for monitoring spatio-temporal changes in vivo. For PK and biodistribution analysis, 0.2 μg/g body weight of Cy5.5–HSA/TIMP-2 was injected into MAT-LyLu prostate tumor xenografts, which were then imaged using an IVIS-200 optical imaging system. To quantify the accumulated HSA/TIMP-2 in tumors, we introduced a standard curve with depth-corrected fluorescence measurement. Results In the vascular tube formation assay with human umbilical vein endothelial cells (HUVECs), Cy5.5–HSA/TIMP-2 showed an antiangiogenic effect. In prostate cancer xenografts, Cy5.5–HSA/TIMP-2 exhibited a prolongation of blood half-life to 19.6 h and relatively preferential distribution to the tumor. The amount of tumor-accumulated Cy5.5–HSA/TIMP-2 was calculated to be 4.5 ± 0.5 ng/g body weight at 2 days, representing 2.25 ± 0.25% of the initial dose. Conclusions We evaluated the pharmacokinetic profile and biodistribution of HSA/TIMP-2 with favorable results, providing new information for more effective approaches to cancer therapeutics using HSA/TIMP-2. Additionally, real-time in vivo fluorescence imaging analysis using a depth-corrected standard curve may serve as a platform to quantify biodistributed drug in anticancer therapeutic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.}, number={3}, journal={Journal of Pharmacy & Pharmaceutical Sciences}, author={Lee, Mi-Sook and Kim, Young Han and Kim, Yeon Joo and Kwon, Seung-Hae and Bang, Jeong-kyu and Lee, Sang-Mok and Song, Yun Seon and Hahm, Dae-Hyun and Shim, Insop and Han, Daeseok and et al.}, year={2011}, month={Oct.}, pages={368–377} }