Pretargeted radioimmunoimaging with a biotinylated D-D(3) construct and (99m)Tc-DTPA-biotin: strategies for early diagnosis of small cell lung cancer

OBJECTIVE: Pro-gastrin releasing peptide (ProGRP) plays an oncogenic role in small cell lung cancer (SCLC). The anti-ProGRP((31-98)) monoclonal antibody D-D(3) can selectively accumulate in SCLC xenografts in nude mice. This study evaluated the effectiveness of a new pretargeting procedure for the early diagnosis of SCLC. METHODS: D-D(3) was radiolabeled with technetium-99m ((99m)Tc) 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. RESULTS: In vivo distribution experiments revealed that (99m)Tc-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-D(3) + avidin + (99m)Tc-DTPA-biotin. Single-photon emission computerized tomography imaging further confirmed that the T/B ratio was highest in this group at all time points. CONCLUSIONS: In contrast to directly labeled D-D(3), pretargeting technology displayed specific enhancement and signal amplification in tumors, which could increase the target tumor uptake of (99m)Tc and provide a new approach for the early diagnosis of SCLC.