Editorial [Hot Topic:Positron Emission Tomography (PET) in Medicinal Chemistry and Drug Discovery (Guest Editor: Ming-Rong Zhang)]

Positron emission tomography (PET) in medicinal chemistry provides a new methodology for drug discovery and molecular imaging. PET has been used for drug research and development by directly assessing both pharmacokinetic and pharmacodynamic events in human and in animals. This issue of Current Topics in Medicinal Chemistry highlights recent developments in the synthesis and application of PET ligands which are of particular importance to pharmaceutical research and molecular imaging. Dr. Mishani from Hadassah Hebrew University (Jerusalem, Israel) describes the PET ligands of the epidermal growth factor receptor (EGFR) for the cancer molecular imaging. Overexpression of the EGFR tyrosine kinase (EGFR-TK) has been demonstrated in numerous human cancers of epithelial origin, and was found to correlate with resistance to treatment and poor prognosis. In this review, the role of EGFR playing in cancer development and therapy is briefly presented, followed by a short review of prominent milestones in the development of EGFR-TK inhibitors. The latter endeavors constitute the fundamental core structure for the development of PET ligands to image the EGFR in vivo. Dr. Furumoto from Tohoku University (Sendai, Japan) reviews the recent advances in the development of amyloid imaging ligands. Excessive amyloid-β (Aβ) deposition in the brain is one of the most crucial events in the early pathological stage of Alzheimer's disease (AD). This review provides an overview of amyloid imaging agents developed until now, and includes: a summary of the fundamental basis and clinical significance of amyloid imaging; lists of binding affinity data for 135 compounds classified into 12 molecular frameworks; a comprehensive discussion of the in vitro and in vivo features of representative Aβ ligands; and a discussion of the current state of clinical evaluation of these amyloid imaging ligands. Dr. Kikuchi from National Institute of Radiological Sciences (Chiba, Japan) describes the development of PET ligands for imaging acetylcholinesterase (AChE) in the cerebral cortex of brain. [11C]MP4A and [11C]MP4P have been developed for clinical studies of the demented disorders including Alzheimer's disease (AD), and these probes have demonstrated not only the reduction of AChE activity in the cerebral cortex of patients with AD but also the inhibitory effects of donepezil and rivastigmine on AChE activity in the brain of AD patients. Following this succession, widely available 18F-labeled analogues of MP4A and MP4P have been developed based on the structure-activity relationships between AChE and piperidinol esters. Dr. Yu from University of Tennessee (Knoxville, TN, USA) describes recent developments of the PET ligands for metabotropic glutamate receptor subtype 5 (mGluR5). MGluR5, a subtype in the group I mGluRs, presents in high density in many brain regions. Investigation of mGluR5 physiological functions under pathologic conditions in patients will be critically important in mGluR5 antagonist's therapy using PET imaging technique. There are eleven mGluR5 imaging PET tracers have been tested in animal studies. This review highlights efforts on the design and development of novel PET ligands for mGluR5 in vivo imaging. Dr. Schou from Karolinska Institute (Stockholm, Sweden) reviews development of radioligands for in vivo imaging of norepinephrine transporter (NET) using PET. The availability of PET ligands for NET may allow researchers to probe the contribution of the NET system to specific brain disorders, such as attention-deficit hyperactivity disorder, substance abuse, AD and Parkinson's disease, and to monitor NET occupancy during treatment with antidepressant drugs. This review summarizes the present status of the development of NET ligands labeled with 11C and 18F. A fluorinated derivative ((S,S)-[18F]FMeNER-D2) of reboxetine has been reported to show better properties over the parent ligand (S,S)-[11C]methylreboxetine for NET.....