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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 34, Number 11
BKCSDE 34(11)
November 20, 2013 
 
Title
 Folate Receptor-Specific Positron Emission Tomography Imaging with Folic Acid-Conjugated Tissue Inhibitor of Metalloproteinase-2
Author
 Sung-Min Kim, Naeun Choi, Seungkyun Hwang, Min Su Yim, Jung-Sik Lee, Sang-Mok Lee, Gyunggoo Cho, Eun Kyoung Ryu*
Keywords
 Folic acid, Human serum albumin-TIMP-2, 68Ga-NOTA-HT2-folate, Tumor, Radioligand
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 radiolabeled compound was prepared for tumor diagnosis by positron emission tomography (PET). 68Ga-NOTAHT2- folate was synthesized from 68Ga 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 68Ga-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.
Page
 3243 - 3248
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