The early detection of primary tumours and metastatic disease is vital for successful therapy and is contingent upon highly specific molecular markers and sensitive, non-invasive imaging techniques. The relationship between platelets and cancer, and the abundance of activated platelets in the tumour microenvironment has been well described. Here we investigate a unique single-chain antibody (scFv), which we generated to specifically target activated platelets, as a novel biotechnological tool for molecular imaging of cancer.
The scFvGPIIb/IIIa, which binds specifically to the activated form of the platelet integrin receptor GPIIb/IIIa present on activated platelets, was conjugated to either Cy7, 64Cu or ultrasound-enhancing microbubbles. Molecular imaging via fluorescence imaging, PET and ultrasound was performed in mice bearing human cancer xenografts to confirm specific targeting of scFvGPIIb/IIIa to activated platelets in the tumour stroma.
Using the scFvGPIIb/IIIa we successfully showed specific targeting of activated platelets within the microenvironment of human breast adenocarcinoma, triple negative breast adenocarcinoma, fibrosarcoma and B cell lymphoma xenograft models via three different molecular imaging modalities. The presence of platelets within the tumour microenvironment, and as such their relevance as a molecular target epitope in cancer was further confirmed via immunofluorescence of human tumour sections of various cancer types, thus validating the translational importance of our novel approach to human disease.
Our study provides proof of concept for the early diagnosis and localisation of tumours by molecular targeting of activated platelets. These findings warrant further investigation of this activated platelet specific scFvGPIIb/IIIa, as a universal marker for cancer diagnosis and further on as a possible theranostic agent, by utilizing a single probe for cancer diagnosis, disease monitoring and targeted therapy.