Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

1 Publication

Development of a F-18-labeled Diaryl-Substituted Dihydropyrrolo[3,2,1-hi]indole as Potential Probe for Functional Imaging of Cyclooxygenase-2 with PET

Gassner, C.; Neuber, C.; Laube, M.; Bergmann, R.; Kniess, T.; Pietzsch, J.


High COX-2 expression is associated with tumor progression and poor treatment response. Imaging of functional COX-2 expression by PET would provide beneficial information for theranostics. Here we describe precursor synthesis and radiolabeling attempts of (dihydro)pyrrolo[3,2,1-hi]indoles [18F]DHPI and [18F]PI, two novel tricyclic COX-2 inhibitors. Contrary to [18F]PI, [18F]DHPI was accessible by [18F]fluorination under mild basic conditions and McMurry cyclization. Radiopharmacological evaluation was performed in vitro by investigating cellular uptake in human COX-2-positive cells, and in vivo in rats and A2058-melanoma xenograft mice, by focusing on metabolic stability and tumor uptake. To assess COX-2 specificity, blocking experiments with celecoxib were performed. Despite of high COX-2 selectivity and metabolic stability, [18F]DHPI did not show COX-2-dependent cell and tissue uptake, in part explained by high unspecific binding. Since appropriate lipophilicity is a prerequisite for targeting intracellularly localized COX-2, future efforts should focus on use of longer-lived radionuclides and/or targeted delivery systems.

Keywords: Cancer; Malignant melanoma; Molecular imaging; Radiochemistry; Selective cyclooxygenase-2 inhibitors; Tumor xenograft models

Involved research facilities

  • PET-Center


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