Development and Evaluation of an 18F-Radiolabeled Monocyclam Derivative for Imaging CXCR4 Expression

In humans, C–X–C chemokine receptortype 4 ( CXCR4) is a protein that is encoded by the CXCR4gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4–CXCL12 interaction in cancer elicits biological activities that result in tumor progressionand has accordingly been the subject of significant investigation for detection and treatment of the disease. Peptidic antagonists have been labeled with a variety of radioisotopes for the detection of CXCR4, but the methodology utilizing small moleculeshas predominantly used radiometals. We report here the development of a 18F-radiolabeled cyclam-based small moleculeradioprobe, [18F]MCFB, for imaging CXCR4expression. The IC50 value of [19F]MCFB for CXCR4was similar to that of AMD3465 (111.3 and 89.8 nM, respectively). In vitro binding assays show that the tracer depicted a differential CXCR4expression, which was blocked in the presence of AMD3465, demonstrating the specificity of [18F]MCFB. Positron emission tomography (PET) imaging studies showed a dis...