Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells.
The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glioblastoma cells, inducing growth promotion. In our study we attempted to target imaging agents to glioblastoma cells via the serotonin receptor. For this we coupled serotonin to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The cellular uptake, cytotoxicity and detection sensitivity of the conjugates were evaluated by confocal laser scanning microscopy (CLSM), cell growth analysis, flow cytometry and magnetic resonance relaxometry on U373 human glioblastoma cells. Receptor-dependency of the uptake was confirmed by competition experiments with excess of unmarked serotonin. Cellular uptake of the conjugates was found in CLSM, magnetic resonance relaxometry and flow cytometry experiments.CLSM revealed the cytoplasmic character of the uptake. In cell growth analysis experiments no adverse effect of either conjugate on the cells was observed. Competition experiments performed with the conjugates and unmarked serotonin showed decreased conjugate uptake compared to the experiments without competition. In conclusion the neurotransmitter serotonin could be successfully used to target imaging agents into human glioblastoma cells. This makes it of interest for future glioblastoma imaging methods.
Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str. 3,72076 Tübingen, Germany. alexsturzu@yahoo.de
Alexander
A
Sturzu
Sumbla
S
Sheikh
Uwe
U
Klose
Hartmut
H
Echner
Hubert
H
Kalbacher
Martin
M
Deeg
Thomas
T
Nägele
Marius
M
Horger
Ulrike
U
Ernemann
Stefan
S
Heckl
D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D005909:Glioblastoma / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D012235:Rhodamines / Q000008:administration & dosage* / Q000737:chemistry; D012701:Serotonin / Q000008:administration & dosage* / Q000737:chemistry
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D012235:Rhodamines; D012701:Serotonin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate