Further important Basic Research Projects of utmost interest


The Division Radiopharmaceutical Chemistry participated in the BMBF-project BIOTRACE Identification and optimization of novel diagnostic radiotracers using biotechnological methods from 2009 to 2012. Together with several industry and academic partners novel peptides and antibody fragments have been isolated from various peptide and antibody libraries by phage or ribosome display. The Division Radiopharmaceutical Chemistry has contributed their highly efficient radiolabeling techniques for antibody fragments and peptides and conducted the whole preclinical characterization of novel candidates in order to evaluate their potential for clinical PET imaging.

Past and ongoing projects and significant accomplishments

Ga-68-labeled recombinant antibody fragments for PET imaging of solid tumors

Immuno-PET imaging of EGFR-expressing tumor xenografts at 1.5 and 3 hours post intravenous injection of a radiolabeled diabody directed against EGFR. The tumor (indicated by arrows) could be clearly visualized at very early time points. The study showed that Ga-68-immuo-PET imaging of solid tumors with recombinant antibody fragments is feasible.
© dkfz.de

The development of genetically engineered single-chain antibody fragments (scFv) consisting of the antibody variable regions provides small sized immunoreactive molecules. As a dimer they have a molecular weight of 50 kDa which still allows rapid penetration into solid tumors while being cleared from the circulation within hours. The aim was to show the feasibility of using these small sized antibody formats for immuno-PET imaging of solid tumors with the short-living radionuclide 68Ga. The scFvs were generated by biopanning on the recombinant extracellular domains of the receptors in cooperation with Affimed Therapeutics AG, Heidelberg. Diabodies and triabodies were formed by genetical engineering. The gentle labeling conditions which were developed during this project, did not affect the affinity and stability of the diabody formats. EGFR and EpCAM positive tumors could be clearly visualized as early as 1 hour after injection into a preclinical mouse model. Along with the advantages of 68Ga, the diabody format in general may exhibit a promising tool for PET imaging to support the patient management during immunotherapy as it may rapidly provide important information regarding.


PET imaging of an antigen expressing tumor using a novel antibody fragment (diabody) developed together with project partner Affimed Therapeutics AG.
© dkfz.de

Besides the successful preclinical imaging with novel biochemical imaging agents, the BMBF-project BIOTRACE led to the development of tools which have high potential to facilitate the preclinical characterization of future candidates deriving from biotechnological selection approaches. Fig. shows the successful PET imaging of an tumor using a novel antibody fragment (diabody) developed by the partner Affimed Therapeutics AG and radiolabeled with Ga-68 in the Division Radiopharmaceutical Chemistry.

Targeting VEGFR-2 for PET imaging of angiogenesis

In a project with the industry partner Sibtech, Inc., USA, two protein-like radiotracers binding vascular endothelial growth factor 2 (VEGFR-2) have been developed. VEGF receptors play a key role in angiogenesis and are important targets for several approved and many experimental drugs. Imaging of VEGF receptor expression in malignant tumors provides important information, which can influence patient management. The developed tracers are based on engineered single-chain VEGF (scVEGF), expressed with cysteine-containing fusion tag (Cys-tag) for site-specific conjugation of PEGylated bifunctional chelating agents, HBED-CC or NOTA, suitable for labeling with Ga-68 at ambient temperature. These radiolabeled probes proved to be promising tracers for the PET imaging of angiogenesis.

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