Non-invasive longitudinal imaging of tumor progression using an 111indium labeled CXCR4 peptide antagonist

摘要

The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductalcarcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approachesmay have diagnostic value in such a challenging, premalignant lesion. The indiumlabeled CXCR4 peptide-antagonist, sup111/supIn-DTPA-Ac-TZ14011, was used tovisualize CXCR4-expression in a mammary intraepithelial neoplastic outgrowth(MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development waslongitudinally monitored using SPET/CT and tracer uptake was compared to uptakein control lesions. Expression of CXCR4 was validated using immunohistochemistryand flow cytometric analysis. The uptake of sup111/supIn-DTPA-Ac-TZ14011 wasrelated to tumor angiogenesis using sup111/supIn-cDTPA-[RGDfK]. Twenty-fourhours after tracer injection, MIN-O lesions could be discriminated from lowCXCR4-expressing control tumors, while the degree of angiogenesis based on theαsubv/subβsub3/sub integrin expression in both tumortypes was similar. The uptake of sup111/supIn-DTPA-Ac-TZ14011 in early MIN-Olesions was significantly lower than in larger intermediate and late-stagelesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively.Intermediate and late stage lesions show a higher degree of membranousCXCR4-staining at immunohistochemistry and flow cytometric analysis. From thisstudy we can conclude that sup111/supIn-DTPA-Ac-TZ14011 can be used tovisualize the CXCR4-expression in MIN-O lesions longitudinally.