A Novel Lily-of-the-Valley Fragrance Contrast Agent for Magnetic Resonance and Fluorescence Imaging of Prostate Cancer Cells

Alexander      Sturzu; Hartmut      Echner; Uwe      Klose; Sumbla      Sheikh; Thomas      Nagele; Christian      Schwentner; Ulrike      Ernemann; Stefan      Heckl

Abstract

Detection of prostate carcinoma metastases is currently performed either via indirect tests like the prostate specific antigen (PSA) or prostate cancer gene 3 (PCA3) or by biopsies from masses found with medical imaging methods. Our goal was to use an ectopic odorant receptor to target prostate-derived cells throughout the body for imaging by magnetic resonance and fluorescence imaging. We synthesized a conjugate containing undecylic aldehyde (an antagonist of the human olfactory receptor hOR17-4), gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (a common magnetic resonance contrast agent) and fluorescein isothiocyanate (a fluorescent dye). Two different prostate cancer cell lines as well as five other different malignant cell lines and healthy prostate epithelial cells were incubated with this conjugate and evaluated by flow cytometry, confocal laser scanning microscopy and magnetic resonance imaging. The prostate- derived healthy and malignant cells showed stronger fluorescence than the non-prostate cancer cell lines in the flow cytometry and confocal laser scanning microscopy experiments. In the magnetic resonance imaging experiments the T1 relaxation time reduction (higher signal intensity) was also stronger for the prostate-derived cells than for the non-prostate cells. The examined conjugate showed high prostate-cell-specificity. This property makes it of potential value in the diagnosis of prostate cancer lymph node metastases.

Keywords: Lily-of-the-valley fragrance receptor, undecylic aldehyde, prostate carcinoma, gadolinium tetraazacyclododecanetetraacetic acid, prostate carcinoma metastases, medical imaging methods, fluorescent dye, magnetic resonance imaging, cancer lymph node metastases, malignant cell, malignant prostate disease, lysine, carcinoma cells, Gd(III)chloride hexahydrate, human cervix carcinoma cells