CXCR4

Background

In oncology the early diagnosis of primary tumors and metastases at the cellular and subcellular level as well as the noninvasive assessment of treatment response using the state-of-the-art imaging technologies PET/CT and PET/MRI is of great clinical interest owing to a resulting high impact on the clinical management of the concerned patient.

It was recently described that the CXC receptor 4/CXC ligand 12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The activation of the CXCR4/CXCL12 pathway in prostate progenitor populations obviously affects the differentiation potential, cell adhesion, clonal growth and tumorigenicity of prostate cancer. Anyhow, the activation of the CXCR4/CXCL12 pathway is also important for other tumor entities.

Past and ongoing projects and significant accomplishments

Ga-68-labeled DOTA-4-FBn-TN14003.
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The project was conducted in collaboration with the Division of Medical Physics in Radiology. The aim of the study was the synthesis, Ga-68-labeling and first evaluation of DOTA-4-FBn-TN14003, an antagonist for the CXCR4 receptor, as a potential PET tracer. The peptide was synthesized using solid phase peptide synthesis and radiolabeling of this versatile precursor was performed with Ga-68, which was obtained from a Ge-68/Ga-68 generator. The inhibition constants (IC50) of Ga-DOTA-4-FBn-TN14003 and 4-FBn-TN14003 to CXCR4 were determined in a competition assay against 125I-SDF-1a using Jurkat as well as MDA-MB-231 cells. The IC50 values of Ga-DOTA-4-FBn-TN14003 (1.99 ± 0.31 nM) and 4-FBn-TN14003 (4.07 ± 1.00 nM) proved to be comparable, indicating negligible influence of the metal complex.

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