Partners and International Organizations
(English)
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AT, BE, CH, CZ, DE, DK, EL, ES, FI, FR, IT, MK, NL, PL, PT, RO, RS, SE, SI, TR, UK
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Abstract
(English)
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The overall goal of this proposal is successful, targeted radionuclide therapy in tumor bearing mice using a folate-based radiotracer. This should be achieved by the design of novel radiofolate conjugates with improved overall pharmacokinetic profiles in order to selectively target cancer cells while minimizing uptake and retention in healthy tissues and organs particularly in the kidneys. For this purpose we will install an albumin binding sequence into folate derivatives in order to reduce the renal excretion of the tracer and to increase tumor uptake. All compounds will be initially characterized in vitro and in vivo with diagnostic amounts of radioacitvity. In parallel we will investigate in vitro the therapeutic approach using radiofolates loaded with different particle-emitting radionuclides such as Cu-67, Ga-67, Tb-161, Lu-177 and Bi-213. For these in vitro experiments we will use our existing folate conjugates equipped with suitable chelating systems. The different tracers/radionuclides will be tested on different FR-positive cancer cells in order to investigate the antiproliferative effect of radiofolates alone and in combination with antifolates. In a second step we plan to translate our experience form in vitro studies to the in vivo situation and perform pre-clinical folate-based radionuclide therapy in tumor bearing mice with the optimal radioconjugate(s) developed. Expected Value of the Proposal: Application of folate-based radionuclide therapy would represent a milestone in the field of FR-targeted therapy. Ovarian cancer is one example of a tumor type that frequently expresse the FR (> 90 % of the cases). This cancer type is the fifth leading cause of cancer death in women. Surgery is the dominant treatment. However, it is only effective for malignant tumors that are well-differentiated and confined to the ovary. Development of alternative therapeutic options for undifferentiated tumors with minimal side effects, e.g. via the use of radionuclde therapy, are therefore of higest interest. For this reason the present proposal fits ideally in the over-all objectives of the recently launched COST Action BM0607 ('TARGETED RADIONUCLIDE THERAPY'.
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