title: Novel bourgeonal fragrance conjugates for the detection of prostate cancer.
abstract: The methods used for detection of prostate cancer and prostate cancer lymph node metastases in medical diagnostics leave room for improvement. Currently, no means of identifying metastasized lymph nodes other than biopsies is available. Markers which are exclusively found on prostate cancer cells present a focal point for potential imaging methods. To complement the established markers like e.g. PCA3-a noncoding mRNA sequence-and PSA-a serine protease-we investigated the ectopically expressed G-protein coupled olfactory receptor OR1D2 as a possible target for prostate-specific detection with its agonist bourgeonal which has been conjugated to two different fluorescent dyes. We performed mRNA expression analysis of the OR1D2 receptor mRNA by reverse transcriptase polymerase chain reaction on LNCaP prostate carcinoma cells and three other non-prostate derived carcinoma cell lines. Additionally, we used flow cytometry to investigate the uptake of fluorescent-dye-bound OR1D2-ligand bourgeonal into the examined carcinoma cell lines. Finally, confocal laser scanning microscopy of in vitro cell culture and in vivo tumor xenografts on mice was performed. We could confirm OR1D2 receptor mRNA overexpression as well as stronger uptake of both bourgeonal conjugates in vitro and in vivo for LNCaP cells compared to the non-prostate derived cell lines. Cytoplasmic accumulation and no adverse effects after in vitro and in vivo application of the conjugates were observed. The conjugates represent a platform for the development of future prostate-specific imaging applications, e.g. detection of metastasized lymph nodes during surgery by intraoperative laser examination.
authors.affiliation: Department of Neuroradiology, University of Tübingen, Hoppe-Seyler-Str.3, 72076, Tübingen, Germany, alexsturzu@yahoo.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sturzu
authors.forename: Sumbla
authors.initials: S
authors.lastname: Sheikh
authors.forename: Hartmut
authors.initials: H
authors.lastname: Echner
authors.forename: Thomas
authors.initials: T
authors.lastname: Nägele
authors.forename: Martin
authors.initials: M
authors.lastname: Deeg
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.forename: Marius
authors.initials: M
authors.lastname: Horger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ernemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Heckl
mesh_terms: D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D019793:Fluorescein / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D010476:Perfume; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics*; D012235:Rhodamines / Q000737:chemistry; D029589:Seminal Plasma Proteins / Q000235:genetics*
chemical_list: D000447:Aldehydes; D005456:Fluorescent Dyes; C473192:OR1D2 protein, human; D010476:Perfume; D012333:RNA, Messenger; D018035:Receptors, Odorant; D012235:Rhodamines; D029589:Seminal Plasma Proteins; C473193:bourgeonal; D019793:Fluorescein