Molecular imaging of radioluminescent nanoparticle probes injected into biological tissue is performed by irradiated the tissue with ionizing radiation to induce radioluminescence at optical wavelengths, preferably at predetermined near infrared wavelengths. The optical light is detected and processed to determine a spatial distribution of the probes. The radioluminescent nanoparticles may be inorganic or organic phosphors, scintillators, or quantum dots. Imaging systems realizing this technique include tomographic systems using an x-ray beam to sequentially irradiate selected regions, systems with a radioactive source producing the ionizing radiation from outside the tissue, such as with a beam, or inside the tissue, such as with an endoscope or injected radiopharmaceutical. The optical signals may be detected by a photodetector array external to the tissue, a photodetector integrated with an endoscope or mammographic paddle, integrated into a capsule endoscope, or an array positioned near the biological tissue.