oa Editorial [Hot topic: Imaging of ABC Transporter Function and Expression (Guest Editors: Nicola Antonio Colabufo and Aren van Waarde)]

ABC transporters play a crucial role in several physiological barriers such as the blood-brain barrier (BBB), bloodcerebrospinal fluid (B-CSF) barrier, and blood-testis barrier (BTB) modulating the absorption and excretion of xenobiotics across these barriers. In the brain, these transporters are localized at the luminal membrane of endothelial cells of blood capillaries where they actively modulate the permeation of xenobiotics. Transporter over-expression has been observed in several tumors causing multidrug resistance (MDR) to treatment with chemotherapeutics. Moreover, resistance to central nervous system (CNS) drugs, such as antidepressant, antiepileptic and anti-HIV medicine, may also be related to overexpression of ABC transporters. Recently, it has been reported that alterations in ABC expression and function are related to the etiology and pathogenesis of neurologic disorders, such as Alzheimer's disease (AD) and Parkinson's (PD) disease. Moreover, a recent study reported that ABC expression and function are strongly decreased during the neuro-inflammation process in Multiple Sclerosis (MS). Positron Emission Tomography (PET) is of great importance for non-invasive studies of physiological and pathological processes in the brain, contributing to a understanding of the etiology of neurological diseases. The tracers used for PET are small molecules belonging to several classes of compounds developed in the medicinal chemistry field. Several in vitro and ex vivo assays can be used to characterize their interaction mechanism with ABC transporters. ABC substrates labeled with positron emitters are tracers for monitoring the activity of these transporters whereas labeled ABC inhibitors may permit to estimate their expression. The first section of this issue is focused on the contribution of medicinal chemistry in developing potent inhibitors, substrates and modulators of various ABC transporters [1-3]. An overview of natural compounds able to modulate such transporters is also provided [4], and innovative strategies for the design of novel radiotracers are discussed [5]. A second section focuses on PET imaging to assess the function of ABC transporters in neurodegenerative diseases [6] in epilepsy [7] and in chemoresistant tumors [8]. Other manuscripts highlight how PET imaging can be used to elucidate mechanisms underlying drug disposition [9,10] and how cerebral tracer uptake can be quantified with compartment models [11]. A final contribution describes SPECT studies of ABC transporter function in oncology [12]. As guest editors, we would like to thank all authors for their comprehensive contributions and the prompt submission of their manuscripts. Moreover, we thank Prof. Allen Reitz, Editor-in Chief of Current Topics in Medicinal Chemistry, for his kind invitation and support.