Poster Presentation Eradicate Cancer 2018

Imaging Activated Platelets in Cancer- An Avenue For Early Cancer Detection and Targeted Therapy. (#119)

May Lin Yap 1 2 , James McFadyen 2 3 4 , Xiaowei Wang 2 3 , Nicholas Zia 5 6 , Jan David Hohmann 2 , Melanie Ziegler 2 , Yu Yao 2 , Alan Pham 7 , Matthew Harris 5 , Paul Donnelly 6 , P Mark Hogarth 1 8 9 , Geoffrey Pietersz 1 2 8 9 , Bock Lim 2 , Karlheinz Peter 2 3 9
  1. Department of Pathology, University of Melbourne, Melbourne, VIC, Australia
  2. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
  3. Department of Medicine, Monash University, Melbourne, VIC, Australia
  4. Department of Hematology, Alfred Hospital, Melbourne, 3004, Australia
  5. Clarity Pharmaceuticals, Sydney, NSW, Australia
  6. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, Australia
  7. Department of Anatomical Pathology, Alfred Hospital, Melbourne, VIC, Australia
  8. Burnet Institute, Melbourne, VIC, Australia
  9. Department of Immunology, Monash University, Melbourne, VIC, Australia

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.   

 

  1. Yap ML, McFadyen JD, Wang X, Zia NA, Hohmann JD, Ziegler M, Yao Y, Pham A, Harris M, Donnelly PS, Hogarth PM, Pietersz GA, Lim B, Peter K. Targeting Activated Platelets: A Unique and Potentially Universal Approach for Cancer Imaging. Theranostics 2017; 7(10):2565-2574.