Project Details
Projekt
Evaluation and application of a novel radioisotope for immuno-PET:Niobium-90
Applicant
Professor Dr. Frank Rösch
Subject Area
Nuclear Medicine, Radiotherapy, Radiobiology
Term
from 2014 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 256296058
A yearly increase in tumor cases worldwide stimulated a fast progression of nuclear medicine in the last decades in the diagnosis and treatment of cancer. One attractive example of a novel diagnosis option is immuno-PET: the tracking and quantification of labeled proteins such as monoclonal antibodies (mAb) with positron emission tomography (PET) at high resolution and sensitivity. Common positron emitters as F-18 (T½ = 110 min), O-15 (T½ = 2.04 min), N-13 (T½ = 9.96 min) and C-11 (T½ = 20.4 min) are practically useless for immuno-PET, because the pharmacokinetics and pharmacodynamics of proteins take from several hours to several days and the physical half-lives of these radioisotopes is too short. This fact calls for the development of new radioisotopes with appropriate characteristics (physical half-life, decay mode) to radiolabel proteins. This project aims to evaluate Nb-90 as an isotope for immuno-PET. Its intermediate half-life of 14.6 hours and the high positron branching (53 %) make it appropriate for quantitative in vivo imaging of antibodies and antibody fragments. In previous studies we showed initial strategies for the preparation of Nb-90-labeled antibodies and their high in vitro stability. The aims of this project are: a.) to improve the production method of the radionuclide, b.) to optimize its radiochemical separation, c.) to investigate appropriate labeling protocols, and d.) to label selected monoclonal antibodies. e.) Finally, the in vivo evaluation of Nb-90 labeled biomolecules is planned. We will evaluate the in vivo behavior of full length antibodies as well of antibody fragments. Three well established PET isotopes will be applied as references, Zr-89 (T½ = 78.4 h) for long pharmacokinetic processes and Ga-68 (T1/2 = 67.7 min) and Sc-44 (T1/2 = 3.92 h) for antibody fragments. To attach the isotopes to biomolecules, the same bifunctional chelator desferrioxamine is considered as the ligand of choice.
DFG Programme
Research Grants
International Connection
Netherlands, Russia
Participating Persons
Dr. Dmitry Filosofov; Professor Dr. Klaus Kopka; Professorin Dr. Danielle Vugts
