A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs were synthesized. Among them, WC-26 and WC-59 were identified as the most potent σ 2 receptor ligands ( K i = 2.58 and 0.82 nM, respectively) with high selectivity against σ 1 ( K i of σ 1/ σ 2 ratio = 557 and 2087, respectively). [ 18F] WC- 59 was radiolabeled via a nucleophilic substitution of a mesylate precursor by [ 18F]fluoride, and in vitro direct binding studies of [ 18F] WC- 59 were conducted using membrane preparations from murine EMT-6 solid breast tumors. The results indicate that [ 18F] WC-59 binds specifically to σ 2 receptors in vitro ( K d = ∼2 nM). Biodistribution studies of [ 18F] WC- 59 in EMT-6 tumor-bearing mice indicated that the tracer was a less suitable candidate for clinical imaging studies than existing F-18 labeled σ 2 receptor ligands. The ability of WC- 26 to enhance the cytotoxic effects of the chemotherapy drug, doxorubicin, was evaluated in cell culture using the mouse breast tumor EMT-6 and the human tumor MDA-MB435. WC- 26 greatly increased the ability of doxorubicin to kill these two tumor cell lines in vitro. These results indicate that WC- 26 is potentially a useful chemosensitizer for the treatment of cancer when combined with conventional chemotherapeutics.