Purpose: A 1 8 fluorine-labeled derivative of vasoactive intestinal peptide [ 1 8 F- Arg 1 5 ,Arg 2 1 VIP( 1 8 F-dVIP)] was evaluated as a potential imaging agent for breast cancer by comparison with 2-deoxy-2-[ 1 8 F]fluoro-D-glucose (FDG) using standard ex vivo determinations and small animal position emission tomography (PET) imaging.Procedures: Human breast carcinomas, T-47D and MDA-MB231, tumor-bearing nude mice were injected intravenously with 1 8 F-dVIP or FDG for imaging and/or biodistribution (ex vivo) determined by gamma counting.Results: FDG had two- to three-fold greater tumor accumulation and target-to-non target contrast relative to 1 8 F-dVIP. VIP receptors were detected in both tumor types but in low concentrations (<15,000 receptors/cell) consistent with lower uptakes. FDG was cleared rapidly from non-target tissues while 1 8 F-dVIP cleared into the kidneys.Conclusions: 1 8 F-dVIP uptake in mice T-47D tumors and kidneys determined by imaging correlated with values determined by ex vivo counting suggesting that tumor and other tissue uptakes can be quantified by in vivo positron projection imaging. (Mol Imag Biol 2002;4:369-379)