Pharmacokinetics and Biodistribution of Human Serum Albumin-TIMP-2 Fusion Protein Using Near-Infrared Optical Imaging

  • Mi-Sook Lee
  • Young Han Kim
  • Yeon Joo Kim
  • Seung-Hae Kwon
  • Jeong-kyu Bang
  • Sang-Mok Lee
  • Yun Seon Song
  • Dae-Hyun Hahm
  • Insop Shim
  • Daeseok Han
  • Song Her

Abstract

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.

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Published
2011-10-01
How to Cite
Lee, M.-S., Kim, Y. H., Kim, Y. J., Kwon, S.-H., Bang, J.- kyu, Lee, S.-M., Song, Y. S., Hahm, D.-H., Shim, I., Han, D., & Her, S. (2011). Pharmacokinetics and Biodistribution of Human Serum Albumin-TIMP-2 Fusion Protein Using Near-Infrared Optical Imaging. Journal of Pharmacy & Pharmaceutical Sciences, 14(3), 368-377. https://doi.org/10.18433/J3H88D
Section
Pharmaceutical Sciences; Review Articles