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http://dx.doi.org/10.5012/bkcs.2013.34.11.3243

Folate Receptor-Specific Positron Emission Tomography Imaging with Folic Acid-Conjugated Tissue Inhibitor of Metalloproteinase-2  

Kim, Sung-Min (Magnetic Resonance Research Center, Korea Basic Science Institute)
Choi, Naeun (Magnetic Resonance Research Center, Korea Basic Science Institute)
Hwang, Seungkyun (Magnetic Resonance Research Center, Korea Basic Science Institute)
Yim, Min Su (Magnetic Resonance Research Center, Korea Basic Science Institute)
Lee, Jung-Sik (Research Institute of BiocurePharm Co. Ltd.)
Lee, Sang-Mok (Research Institute of BiocurePharm Co. Ltd.)
Cho, Gyunggoo (Magnetic Resonance Research Center, Korea Basic Science Institute)
Ryu, Eun Kyoung (Magnetic Resonance Research Center, Korea Basic Science Institute)
Publication Information
Bulletin of the Korean Chemical Society / v.34, no.11, 2013 , pp. 3243-3248 More about this Journal
Abstract
The tissue inhibitor of metalloproteinase-2 (TIMP-2) inhibits matrix metalloproteinases activity and modulates cellular proliferation and apoptosis. The human serum albumin-TIMP-2 with folic acid conjugate (termed HT2-folate) was synthesized to promote uptake through folate receptors (FRs), and a corresponding radio-labeled compound was prepared for tumor diagnosis by positron emission tomography (PET). $^{68}Ga$-NOTA-HT2-folate was synthesized from $^{68}Ga$ and the NOTA chelator with HT2-folate. The fusion protein was identified using MALDI-TOF mass spectrometry. The radioligand was prepared with a high radiochemical yield. Cell-surface association of $^{68}Ga$-NOTA-HT2-folate significantly increased over time in FR-positive tumor cells. In animal PET and biodistribution studies, tumor uptake was very high as early as 1 h after radioligand injection. Folate conjugation enhanced the selective receptor-targeting efficacy of HT2 in FRexpressing tumors, and its radioligand will be useful as an in vitro tool and for in vivo tumor diagnosis by PET imaging.
Keywords
Folic acid; Human serum albumin-TIMP-2; $^{68}Ga$-NOTA-HT2-folate; Tumor; Radioligand;
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