Pretargeted radioimmunoimaging with a biotinylated D-D3construct and99mTc-DTPA-biotin: strategies for early diagnosis of small cell lung cancer

Abstract

ObjectivePro-gastrin releasing peptide (ProGRP) plays an oncogenic role in small cell lung cancer (SCLC). The anti-ProGRP(31-98)monoclonal antibody D-D3can selectively accumulate in SCLC xenografts in nude mice. This study evaluated the effectiveness of a new pretargeting procedure for the early diagnosis of SCLC.MethodsD-D3was radiolabeled with technetium-99m (99mTc) using a three-step pretargeting method. Mice with SCLC xenografts were treated with different labeling regimens, and the biodistribution and radioimmunoimaging were explored. The percentage injected dose per gram (%ID/g) in various organs, tumor/non-tumor (T/NT) ratio, and tumor/background (T/B) ratio were also calculated.ResultsIn vivo distribution experiments revealed that99mTc-DTPA-biotin was metabolized in the liver and kidney, with rapid elimination in the blood. The T/B ratio was highest in mice treated with biotinylated antibody D-D3 + avidin + 99mTc-DTPA-biotin. Single-photon emission computerized tomography imaging further confirmed that the T/B ratio was highest in this group at all time points.ConclusionsIn contrast to directly labeled D-D3, pretargeting technology displayed specific enhancement and signal amplification in tumors, which could increase the target tumor uptake of99mTc and provide a new approach for the early diagnosis of SCLC.