The lily-of-the-valley fragrance receptor--potential in prostate cancer imaging.
BACKGROUND
The early diagnosis of prostate cancer and its metastases still remains a great challenge. Recently, olfactory receptors have been found in healthy and malignant prostate tissue. If conjugated to a dye, olfactory receptor ligands would represent candidates for markers of not only olfactory cells but also prostate tissue. Such a conjugate would be of great value for the detection of prostate cancer metastases.


METHODS
We coupled sulforhodamine, a fluorescence dye, to undecylic aldehyde, the antagonist of the lily-of-the-valley fragrance receptor. By using confocal laser scanning microscopy and flow cytometry we examined the uptake of this conjugate into various different human cell lines. One healthy prostate cell line, two different prostate carcinoma cell lines, and five other carcinoma cell lines were investigated. CD1 nude mice bearing human PC3 prostate carcinoma xenografts were injected with the conjugate. Rhodamine fluorescence of mouse organ frozen sections was evaluated by confocal laser scanning microscopy.


RESULTS
When comparing the seven human cell lines, the conjugate was preferentially taken up by the cytoplasm of healthy and malignant prostate cells. The mice showed high conjugate uptake into the xenografts, but much lower uptake into the mouse organs. After 3 hr of circulation, efflux could be observed in the xenograft sections. Xenograft touch prints confirmed in vivo intracellular accumulation.


CONCLUSIONS
This conjugate may be of potential value in the diagnosis of prostate cancer and its metastases.
Sturzu
Alexander
A
Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany. alexsturzu@yahoo.de
Echner
Hartmut
H
Heckl
Stefan
S
D000447:Aldehydes / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D018035:Receptors, Odorant / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012235:Rhodamines / Q000737:chemistry* / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous
D000447:Aldehydes; D005456:Fluorescent Dyes; D018035:Receptors, Odorant; D012235:Rhodamines; C022027:lissamine rhodamine B