TY - JOUR
T1 - Preclinical In Vitro and In Vivo Evaluation of [18F]FE@SUPPY for Cancer PET Imaging
T2 - Limitations of a Xenograft Model for Colorectal Cancer
AU - Balber, T
AU - Singer, J
AU - Berroterán-Infante, N
AU - Dumanic, M
AU - Fetty, L
AU - Fazekas-Singer, J
AU - Vraka, C
AU - Nics, L
AU - Bergmann, M
AU - Pallitsch, K
AU - Spreitzer, H
AU - Wadsak, W
AU - Hacker, M
AU - Jensen-Jarolim, E
AU - Viernstein, H
AU - Mitterhauser, M
N1 - Funding Information:
This work was supported by the Austrian Science Fund (FWF P26502-B24, M. Mitterhauser) and was performed with the support of the Molecular Imaging Cluster of the Medical University of Vienna, Austria. J. Fazekas-Singer was supported by Grant CCHD W1205-B09 awarded to Dr. E. Jensen-Jarolim.
Publisher Copyright:
© 2018 T. Balber et al.
PY - 2018
Y1 - 2018
N2 - 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 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, 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 hA3AR expression and was subsequently chosen as tumor graft. 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 insufficient 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.
AB - 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 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, 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 hA3AR expression and was subsequently chosen as tumor graft. 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 insufficient 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.
KW - Animals
KW - Colorectal Neoplasms/diagnostic imaging
KW - Fluorine Radioisotopes
KW - HT29 Cells
KW - Heterografts
KW - Humans
KW - Mice
KW - Molecular Imaging/methods
KW - Neoplasm Proteins/analysis
KW - Nicotinic Acids/pharmacokinetics
KW - Positron-Emission Tomography/methods
KW - Radiopharmaceuticals/pharmacokinetics
KW - Receptor, Adenosine A3/analysis
UR - http://www.scopus.com/inward/record.url?scp=85062599464&partnerID=8YFLogxK
U2 - 10.1155/2018/1269830
DO - 10.1155/2018/1269830
M3 - Journal article
C2 - 29666562
SN - 1555-4309
VL - 2018
SP - 1269830
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
M1 - 1269830
ER -