Cerenkov Luminescence Imaging at a Glance

Cerenkov luminescence imaging (CLI) is a new technique that has rapidly gained great interest in the molecular imaging field bridging optical imaging and nuclear medicine. Based on the detection of Cerenkov radiation (CR) in biological tissue, in only five years many different applications of CLI were developed spanning from cancer imaging to Alzheimer's disease and many different approaches were tested in order to increase its potentialities. In particular some efforts were made to transform CLI from a planar imaging technique into a tomographic technique or to shift the CR in a red-infrared radiation more suitable for biological applications. Moreover CLI, developed as a preclinical investigation, has obtained very quickly, interesting results on humans. Here we present a schematic and brief overview of the CLI landscape in order to show the principal results and applications to the biology. More precisely we focused on the potentialities of optical detection of ra- diotracers excluding the application of Cerenkov radiation obtained with the use of external radiation beam. Cerenkov luminescence imaging (CLI) has been recently introduced in the Optical Imaging (OI) landscape as a new pre-clinical imaging tool to investigate much pathology in vivo. It is based on the detection of light produced by high energy charged particle (like electron or positron) moving faster than the speed of light in a dielectric medium. When travelling in the medium the particle can polarize the sur- rounding molecules and, when they relax back, they can emit light in the form of radiation luminescence. This is the so- called Cerenkov radiation (CR). It occurs if the energy of the particle is greater than a threshold that is around 220 keV in biological tissues. The CR spectrum consists of continuous wavelengths throughout the ultraviolet, visible and near in- frared range. The intensity distribution is inversely propor- tional to the square of the wavelength. The emitted photons can be detected by a variety of light sensitive detectors, like photomultipliers, highly sensitive charge-coupled device (CCD), and others. CR was discovered by Pavel Alek- seyevich Cerenkov in 1932 and the theoretical analysis of the experimental data was provided by Frank and Tamm in 1937 (1). Due to faint emission the detection in biological tissues was very challenging. A very preliminary attempt was made by Burch in 1971 (2); he detected CR in human eye tumors treated with 32P with a photomultiplier tube, but this method was not employed subsequently and no imaging was performed. For a real imaging of CR emitted by tissues we had to wait for about 40 years. Now different applica- tions of CLI were developed and many efforts were done in order to increase the potentialities of the technique. In this review our goal was to present almost all the studies referred to CLI in biomedical field and we tried to organize them in one table (Table 1) for a fast consultation. In the table the