Cholin analogs as potentional diagnostics/therapeutics for prostate cancer

Konference: 2015 XI. Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Onkologická diagnostika

Téma: Protinádorová léčiva a postupy II

Číslo abstraktu: 021

Autoři: Dr. Zbyněk Nový, Ph.D.; Dr. Miloš Petřík, Ph.D.; Ing. Pavel Švec; Mgr. Martin Hrubý, Ph.D.; Mgr. Martina Michalová; Mgr. Barbora Lišková, Ph.D.


Cholin is a physiological substrate for synthesis of lecithin which is the crucial component of cell membranes. As tumor cells are dividing rapidly their uptake of cholin is significantly increased. Due to this phenomenon fluorine-18 labelled cholin is already used as a positron emmision tomography (PET) tracer for imaging of prostate cancer in clinics. We are testing various cholin analogs as a potentional new tumor tracers based on this knowledge. Our goal is to reveal (in vitro) suitable candidates for in vivo testing. In our case we plan to replace fluorine-18 labelling with various iodine isotopes, what allows us to use such labelled analogs as diagnostic tracers as well as therapeutics or even as so called theranostic agents.


At first we have examinated six different cell lines (PC3, DU145, LNCAP, MATLYLU, BJ, MRC5) for choline uptake in vitro in order to determine the most suitable cell line for further studies. Then we have performed in vitro experiments to establish IC50 values for studied choline derivatives. Studied compounds competed in uptake with tritium labelled choline (as natural substrate) which was mesured using beta scintilation analyzer. Adationally four preclinical ADME tests have been done to determine plasmatic and microsomal stability, plasma protein binding and permeability of cholin analogs.

Results and conclusions

We have chosen PC3 prostate cancer cell line as a model for our IC50 experiments, because of the highest uptake of radiolabelled choline derivative into this cell line compared to other widely used prostate cancer modeling cell lines. Eighteen different choline analogs were tested for their IC50 values. Four of them revealed almost as suitable IC50s like natural substrate (choline). This four candidates selected for further in vivo testing have shown also a useful ADME properties i.e. high plasma and microsomal stability, low plasma protein binding and high artificial membreane permeability (PAMPA). We can conclued that this four compounds are promising candidates for in vivo testing as prostate cancer tracers/therapeutics.

Datum přednesení příspěvku: 3. 12. 2015