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Wang, Susan; Luo, Jin; Lantrip, Douglas A; Waters, David J; Mathias, Carla J; Green, Mark A; Fuchs, Philip L; Low, Philip S
Bioconjugate chemistry, 09/1997, Letnik: 8, Številka: 5Journal Article
Folate-conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress folate receptors. In a previous study, folic acid was linked through its γ-carboxyl group to deferoxamine (DF), and the 67Ga-labeled complex (67GaDF−folate) was examined for in vivo tumor targeting efficiency in athymic mice with a human tumor cell implant. Although superb tumor-to-background contrast was obtained, slow hepatobiliary clearance would compromise imaging of abdominal tumors such as ovarian cancer. In the present study, folic acid was conjugated to an alternative chelator, diethylenetriaminepentaacetic acid (DTPA), via an ethylenediamine spacer. The desired DTPA−folate(γ) regioisomer was synthesized by two different approaches, purified by reversed phase column chromatography, and characterized mainly by analytical HPLC, mass spectroscopy, and NMR. In cultured tumor cells, uptake of 111InDTPA−folate(γ) was found to be specific for folate receptor-bearing cells, and the kinetics of uptake were similar to those of free folate and other folate-conjugated molecules. In the normal rat, intravenously administered 111InDTPA−folate(γ) was found to be rapidly excreted into the urine, giving intestinal levels of radiotracer 10-fold lower than those observed with 67GaDF−folate(γ) at 4 h. In a preliminary mouse imaging study, a folate receptor-positive KB cell tumor was readily visualized by γ scintigraphy 1 h following intravenous administration of 111InDTPA−folate(γ).
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