Synthesis and evaluation of a 99mTc-labeled chemokine receptor antagonist peptide for imaging of chemokine receptor expressing tumors

Abstract

ObjectiveThe chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. In the present study, we report on the evaluation of a new radiopharmaceutical peptide for its potential to visualization for CXCR4-expressing tumors in vivo. MethodsA CXCR4 antagonist analogue was synthesized using a standard Fmoc solid phase strategy and labeled with 99mTc via HYNIC and EDDA/tricine as coligands. In addition, stability in human serum, receptor binding internalization, in vivo tumor uptake, and tissue biodistribution were evaluated. Labeling procedure has been accomplished at 100 °C. RTLC and HPLC analysis methods have been used to confirm the procedure. The receptor binding internalization rate studied using B16-F10 melanoma tumor cells. C57BL/6 mice bearing B16-F10 tumor were used for radiopeptide biodistribution studies. ResultsLabeling yield of >95% (n=3) was obtained corresponding to a specific activity of 123±60GBq/μmol. Efficient stability in the presence of human serum was observed. The radioligand showed specific internalization (of total add) into B16-F10 cells (1.57±0.27% at 2h). In animal biodistribution study, the uptake in mouse tumor was 2.74±0.47%ID/g after 15min (percentage of injected dose per gram of tissue). ConclusionResults of this study show that labeled peptide conjugate could be a potential candidate for diagnosis of malignant tumors.