Pharmacokinetics and Biodistribution of Human Serum Albumin-TIMP-2 Fusion Protein Using Near-Infrared Optical Imaging
- Authors
- Lee, Mi-Sook; Kim, Young Han; Kim, Yeon Joo; Kwon, Seung-Hae; Bang, Jeong-Kyu; Lee, Sang-Mok; Song, Yun Seon; Hahm, Dae-Hyun; Shim, Insop; Han, Daeseok; Her, Song
- Issue Date
- Jul-2011
- Publisher
- CANADIAN SOC PHARMACEUTICAL SCIENCES
- Citation
- JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, v.14, no.3, pp 368 - 377
- Pages
- 10
- Journal Title
- JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
- Volume
- 14
- Number
- 3
- Start Page
- 368
- End Page
- 377
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13017
- DOI
- 10.18433/J3H88D
- ISSN
- 1482-1826
- 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 mu g/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.
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