Author/Authors :
Balber, T Medical University of Vienna - Vienna, Austria , Singer, J Medical University of Vienna - Vienna, Austria , Berroterán-Infante, N Medical University of Vienna - Vienna, Austria , Dumanic, M Medical University of Vienna - Vienna, Austria , Fetty, L Medical University of Vienna - Vienna, Austria , Fazekas-Singer, J Medical University of Vienna - Vienna, Austria , Vraka, C Medical University of Vienna - Vienna, Austria , Nics, L Medical University of Vienna - Vienna, Austria , Bergmann, M Department of Surgery - Surgical Research Laboratories - Medical University of Vienna - Vienna, Austria , Pallitsch, K University of Vienna - Vienna, Austria , Spreitzer, H Department of Pharmaceutical Chemistry - Faculty of Life Sciences - University of Vienna - Vienna, Austria , Wadsak, W Medical University of Vienna - Vienna, Austria , Hacker, M Medical University of Vienna - Vienna, Austria , Jensen-Jarolim, E Medical University of Vienna - Vienna, Austria , Viernstein, H Department of Pharmaceutical Technology and Biopharmaceutics - Faculty of Life Sciences - University of Vienna - Vienna, Austria , Mitterhauser, M Medical University of Vienna - Vienna, Austria
Abstract :
Molecular imaging probes such as PET-tracers have the potential to improve the accuracy of tumor characterization by directly
visualizing the biochemical situation. Tus, molecular changes can be detected early before morphological manifestation. The
A3 adenosine receptor (A3AR) 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 [
18F]FE@SUPPY
as a PET-tracer for CRC using in vitro imaging and in vivo PET imaging. First, afnity and selectivity of FE@SUPPY and its
metabolites were determined, proving the favorable binding profle of FE@SUPPY. The human adenocarcinoma cell line HT-29
was characterized regarding its hA3AR expression and was subsequently chosen as tumor graf. Promising results regarding the
potential of [
18F]FE@SUPPY as a PET-tracer for CRC imaging were obtained by autoradiography as ≥2.3-fold higher accumulation
of [
18F]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 insufcient tumor uptake due to (1) poor conservation of target expression in xenografts
and (2) unfavorable pharmacokinetics of [
18F]FE@SUPPY in mice. We therefore conclude that HT-29 xenografts are not adequate
to visualize hA3ARs using [
18F]FE@SUPPY.
