Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose

Oncotarget
Shaobo YaoFang Li

Abstract

This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-(18)F-fluoroethyl-β-D-lactose ((18)F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. In this study, a multifunctional module was employed for the automated synthesis of (18)F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. The synthesis of (18)F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. (18)F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. (18)F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. (18)F-FEL has a high binding property t...Continue Reading

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