Small-animal positron emission tomography as a tool for neuropharmacology  Sophie Lancelot, Luc Zimmer  Trends in Pharmacological Sciences  Volume 31, Issue 9, Pages 411-417 (September 2010) DOI: 10.1016/j.tips.2010.06.002 Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 1 Schematic representation of the principle underpinning PET. (a) The cyclotron, a particle (protons or deuterons) accelerator, creates the positron-emitting radionuclides. Positron-emitting radionuclides are typically isotopes such as oxygen-15 (15O), nitrogen-13 (13N), carbon-11 (11C) and fluorine-18 (18F) with short half-lives of 2, 10, 20 and 110min, respectively. (b) These radionuclides are incorporated into molecules during the radiosynthesis step giving the radiotracer after radiopharmaceutical controls. (c) PET scans are acquired following intravenous injection of the radiotracer. The radiotracer accumulates in the tissue to be studied, and its radionuclide decays by emission of a positron (anti-electron). After travelling at most a few millimetres, a positron will collide with an electron, simultaneously releasing two gamma rays (photons) with an energy of 511 keV into opposite directions. These two photons are detected by the PET camera and simultaneously localized within a fixed period of time by a series of opposing detectors, which correspond to multiple rings of scintillation crystals. (d) By collecting a statistically significant number of radioactive events, mathematical algorithms reconstruct a three-dimensional image that shows the distribution of the positron-emitting molecules in the brain. Trends in Pharmacological Sciences 2010 31, 411-417DOI: (10.1016/j.tips.2010.06.002) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 2 Comparison of in vitro autoradiographic and in-vivo microPET images showing the distribution of the 5-HT1A receptor radiotracer [18F]MPPF. (a) Transverse level across the rat hippocampus (CA1, CA2, CA3, cornu ammonis; DG, dentate gyrus). Scale bar: 5mm. (b) In vitro autoradiography at the same level obtained with a spatial resolution of 100μm. Note the high density of radiotracer binding sites in the hippocampus. (c) MicroPET image of an anaesthetized rat, 0–60min after the intravenous injection of [18F]MPPF. The spatial resolution is 1.7mm. Note the superimposition of a 7-T MRI image (Zimmer L., unpublished observations). Trends in Pharmacological Sciences 2010 31, 411-417DOI: (10.1016/j.tips.2010.06.002) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 3 Contributions of PET imaging during the preclinical (basic research) and clinical phases of research (clinical research) to the development of a drug that works on the central nervous system. Trends in Pharmacological Sciences 2010 31, 411-417DOI: (10.1016/j.tips.2010.06.002) Copyright © 2010 Elsevier Ltd Terms and Conditions