Anti-kanker therapie versterkt door kleine radioactief gelabelde compounds met affiniteit voor necrosis (sRALNAC): een Prrof-of-Principle experiment ter ondersteuning van een nieuw patent aanvraag.

The promoters of this project have been active in combating cancers. They have pioneered research in tumor radiofrequency ablation (RFA) with a patent granted to K.U.Leuven, and also studied photodynamic therapy (PDT) and vascular targeting agents (VTAs) for experimental oncology. Despite encouraging results with RFA, PDT and VTAs to induce therapeutic tumor necrosis, sporadic or marginal residues are frequently attributed to tumor incomplete treatment and relapse. We thus propose a potential solution to this problem by extending our patented necrosis avid contrast agents or NACAs from diagnostic to therapeutic applications. Unlike monoclonal antibodies (MW>20kD) used in tumor necrosis treatment (TNT) with poor target-to-liver ratios of less than 1.0 in vivo, small radiolabelled necrosis-avid compounds (SRaLNACs, MW<1-2kD) of a much higher target-to-nontarget ratio will be produced and applied in combination with any necrosis-inducing anticancer therapies to synergistically augment anticancer efficacy. With combined expertise in pharmaceutical R&D, biomedical imaging, and radiopharmacy within K.U.Leuven, this proof-of-concept project aims to considerably reduce tumor relapse rates with contemporary therapies by developing a novel anticancer strategy. Experiments will be carried out to 1) produce animal models of liver tumor to mimic hepatic metastasis in patients; 2) treat the tumor with VTAs and RFA to create tumor necrosis; 3) label NACAs such as hypericin with therapeutic radionuclides such as iodine-131 to form a SRaLNAC; 4) target the tumor necrosis by iv injection of a SRaLNAC; 5) irradiate the residual tumor in the vicinity of tumor necrosis with locally accumulated STaLNAC, and 6) noninvasively monitor therapeutic effects with imaging techniques. The endpoint of improved tumor local control and higher curability can be expected from this comprehensive therapy that logically combines a primary attack to cause bulky tumor necrosis and a secondary targeted radiotherapy to eliminate any residual viable tumor cells. Integriting our previous successful research outputs, this project with expected positive results will exert a primary levering effect on generation of new patent(s) and valorization of certain K.U.Leuven intellectural property by providing direct evidence to strengthen patent claims of our current patent application and creating added values for our NACAs and RFA patents of both diagnostic and therapeutic utilities. Upon project completion with the predicted positive outcomes, the secondary multiplying effects could be anticipated.

Keywords:Liver tumor, Radiofrequency ablation, Vascular targeting agent, Targeted radiotherapy, Radiolabelled compounds, Animal model, Patent, Anticancer therapies

Disciplines:Medical imaging and therapy, Morphological sciences, Oncology, Other biological sciences