Multimodality molecular imaging with activatable fluorescence and radioscintigraphy for specific and quantitative targeted cancer detection

Objectives Multimodality imaging has potential for combining the advantages of different imaging methods. Nuclear imaging is quantitative but cannot separate unbound from bound signal to the specific target. In contrast, optical imaging is difficult to quantify due to its poor tissue penetration, but it is superior to nuclear imaging for target-specificity because it can employ target-specific activation leading to very high target to background ratios. In this study, multimodality imaging employing both activatable fluorescence and radioscintigraphy is demonstrated in a single targeted molecular imaging probe.

Methods A monoclonal antibody, trastuzumab (anti-HER2) was labeled with 111In and ICG. The immunoreactivity was tested using 3T3/HER2 cells. Fluorescence activation was investigated by a phantom study and by in vitro microscopy. The labeled antibody was tested in vivo in both HER1 and HER2 tumor bearing mice. The optical and nuclear images were obtained over 6 days after injection.

Results The immunoreactivity of the dual-labeled probe was 75%. The fluorescence quenching capacity was 7.3 fold. In vitro microscopy demonstrated no fluorescence signal when the probe was bound to cell surface antigens. After the probe was internalized into the cells, it showed bright fluorescence signal. In vivo multimodality imaging revealed that only the target specific tumor was visualized by optical imaging. Meanwhile, the biodistribution profile of the injected antibody was provided by nuclear imaging.

Conclusions We characterized molecular targets using activatable optical moiety, and visualized and quantified the delivery of the targeted antibody using radiolabeled moiety. We demonstrate a dual modality targeted molecular imaging probe that combines very high tumor to background ratios (optical imaging) and quantitation (radionuclide imaging) which could have broad clinical and research applications