Abstract
1459
Objectives: To determine the relationship between PET tracer uptake and gene expression profile, whole genome DNA chip analysis was performed and compared with the results of cell tracer uptake. Methods: Three prostate cancer cell lines: DU145, LNCAP and PC3, and two normal prostate cell lines were studied. 3H-choline was used in the in vitro tracer uptake study. Uptake of cancer cells was measured after one hour of incubation with tracer-containing media. For gene expression analysis, total genomic RNA was extracted from parallel lysates of each cultured cell type and assayed using the Affimetrix whole-genome DNA chip. Our initial assessement focused on the transporter genes and pathways expected to be relevant to uptake of Choline. Results: Percent of tracer uptake/cell (106) of the DU145,. LNCAP and PC3 were 5.62±0.35, 14.14±0.77 and 7.81±0.53 respectively. Facilitated choline transporter (CHT1) messenger RNA was not present in any of the cell lines investigated in this study. On the other hand Choline transporter like protein (CTL) mRNA was present in all cell lines. SCL22A4 mRNA, a member of cation transporter family was present in DU145 and PC3. Choline kinase, choline phosphotransferase, and phospholipase C mRNA were clearly present in all cancer cell lines and the mRNA expression levesl were significantly higher than normal control cells. Conclusions: Our results suggest that facilitated choline transporter (CHT1) is less important than other choline transport systems in the uptake of radio-choline into prostate cancer. Significant overexpression of several kinases for phosphocholine metabolism suggests these enzymes have an association with malignant transformation of the tumor. Full genomic analysis of tumors is now feasible and may become important as a means for tailoring the optimal PET radio tracer to each specific patient.
- Society of Nuclear Medicine, Inc.