Synthesis, radiolabeling, in vitro and in vivo evaluation of heterobivalent peptidic ligands for an improved and specific PET imaging of human breast carcinomas

• Applicant: Professorin Dr. Carmen Wängler
• Subject Area: Pharmacy ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255841900

Aim of the project is the development of heterobivalent peptidic ligands that show a high affinity for both GRP (gastrin releasing peptide) as well as NPY(Y1) (neuropeptide Y1) receptors as it was shown, analyzing human biopsies, that human breast cancers and their metastases exhibit a very heterogeneous receptor expression profile while in most cases exhibiting a sufficient density of at least one of these receptors which would allow for a successful PET imaging of the lesions. Thus, a conjugate of two peptides, one binding to the GRPR and the other binding to the NPY(Y1)R, should result in a heterobivalent compound that allows for the in vivo visualization of most human breast carcinomas. This would strongly improve the specific receptor-mediated breast cancer imaging with PET.Thus, different heterodimers binding to the GRPR as well as the NPY(Y1)R will be synthesized, radiolabeled and systematically evaluated regarding their biological activity (binding affinity to both receptors, tumor cell binding and internalization) to determine structure-activity-relationships for these heterodimers and those conjugates that are suitable in an in vivo tumor imaging application.In order to show that this heterodimerization approach is able to result in radiotracers with improved in vivo tumor targeting properties and pharmacokinetics, the derivatives giving the best results in the in vitro assays will finally be evaluated in vivo in a tumor-bearing mouse model in a µPET/CT study and compared to the monomeric reference compounds.

• DFG Programme: Research Grants