Postoperative Radiotherapy using Engineered Constructs to Capture Radiotherapeutics for Intracavitary Delivery
 
The objective of WP4 is to exploit the engineered TCO tag to capture locally applied radiotherapeutics after intraoperative image-guided surgery. The work involves a two-step process of firstly targeting with the (ZW800-1-cRGD-TCO) construct followed by capture and delivery of the radionuclide compound. In combination with precision surgery (WP3) to obtain the clear margins, our aim is to show that postoperative radiotherapy can a) improve upon further the survival rates than with surgery alone; b) improve target-to-non-target concentration ratio of the radionuclide and c) that we can increase therapeutic radiation dose to the tumour without increasing the radiation dose to normal organs (especially the kidneys). The essential feature of having two stages of targeting is that delivery of the fluorescent probe is separated from delivery of the radiolabeled probe. This makes it possible to independently optimize the targeting construct and the radiolabeled probe to further improve upon the efficiency of surgery by preventing relapse.

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