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Molecular imaging probes such as PET-tracers have the potential to improve the accuracy of tumor characterization by directly visualizing the biochemical situation. Thus, molecular changes can be detected early before morphological manifestation. The A 3  adenosine receptor (A 3 AR) is described to be highly expressed in colon cancer cell lines and human colorectal cancer (CRC), suggesting this receptor as a tumor marker. The aim of this preclinical study was the evaluation of [ 18 F]FE@SUPPY as a PET-tracer for CRC using  in vitro  imaging and  in vivo  PET imaging. First, affinity and selectivity of FE@SUPPY and its metabolites were determined, proving the favorable binding profile of FE@SUPPY. The human adenocarcinoma cell line HT-29 was characterized regarding its hA 3 AR expression and was subsequently chosen as tumor graft. Promising results regarding the potential of [ 18 F]FE@SUPPY as a PET-tracer for CRC imaging were obtained by autoradiography as ≥2.3-fold higher accumulation of [ 18 F]FE@SUPPY was found in CRC tissue compared to adjacent healthy colon tissue from the same patient. Nevertheless, first  in vivo  studies using HT-29 xenografts showed insufficient tumor uptake due to (1) poor conservation of target expression in xenografts and (2) unfavorable pharmacokinetics of [ 18 F]FE@SUPPY in mice. We therefore conclude that HT-29 xenografts are not adequate to visualize hA 3 ARs using [ 18 F]FE@SUPPY.

contrast media and molecular imaging/contrast media and molecular imaging

Preclinical In Vitro and In Vivo Evaluation of [18F]FE@SUPPY for Cancer PET Imaging: Limitations of a Xenograft Model for Colorectal Cancer