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

摘要

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.