We demonstrate fluorescence-enhanced optical imaging of single and multiple fluorescent targets within a large (approximately 1081 cm3) phantom using frequency-domain photon migration measurements of fluorescence collected at individual points in response to illumination of excitation light at individual points on the boundary. The tissue phantom was filled with a 1% lipid solution with and without 0.01 microM Indocyanine Green (ICG) and targets consisted of vials filled with the 1% lipid containing 1-2.5 microM ICG. Measurements were acquired using a modulated intensified CCD imaging system under different experimental conditions. For 3-D image reconstruction, the gradient-based penalty modified barrier function (PMBF) method with simple bounds constrained truncated Newton with trust region method (CONTN) was used. Targets of 0.5, 0.6, and 1.0 cm3 at depths of 1.4-2.8 cm from the phantom surface were tomographically reconstructed. This work demonstrates the practicality of fluorescence-enhanced tomography in clinically relevant volumes.