Positron Emission Tomography: Applications In Drug Discovery and Drug Development

Abstract

Positron Emission Tomography (PET) is a sophisticated nuclear imaging modality that affords researchers the ability to conduct both functional and molecular imaging on biological and biochemical processes in vivo. In functional imaging, biological parameters such as metabolic rate and perfusion that can be altered by disease or treatment are monitored. In molecular imaging, PET can be used to examine and quantify cellular events such as cell trafficking, receptor binding and gene expression. Therefore, PET is an important tool to elucidate mechanisms associated with diseases and drug actions. In addition to PET, microPET is designed to image small animals. A great tool to facilitate preclinical studies and basic research, it can eliminate the need of sacrificing the animal by enabling noninvasive, longitudinal, and serial studies. The results from preclinical studies using microPET can be directly correlated with clinical studies using PET, thus bridging the chasm that used to separate the 2 pivotal phases in drug development. This review first describes the basic principles of PET and compares it to other imaging modalities. Then, PET procedures and PET isotopes and tracers synthesis are outlined. Next, functional and molecular PET imaging applications in the fields of oncology, neurology, and cardiology in both humans and animals are presented. Spanning a wide range, these applications demonstrate the versatility of PET and how it can be used to accelerate drug discovery and development. Finally, the advantages and limitations of PET and how it can be used in the future to minimize risks of drug development are discussed.

Efficacy of PHA-848125, a Cyclin-Dependent Kinase Inhibitor, on the K-RasG12DLA2 Lung Adenocarcinoma Transgenic Mouse Model: Evaluation by Multimodality Imaging

“…In recent years, preclinical imaging techniques such as small-animal magnetic resonance imaging (MRI) and small-animal positron emission tomography (PET; refs. 8, 9) have been used in oncology research for in vivo evaluation of tumors and to assess response to therapy (10)(11)(12)(13).…”

New developments in imaging and functional biomarker technology for the assessment and management of cancer patients

“…Preclinical small-animal imaging devices, such as with micro-PET/CT/SPECT/MRI, have become an integral part of translational research in oncology [14,15,30,33,34,[36][37][38][39]. Since the trend is towards such translational research relying more and more heavily upon imaging end points, the use of these noninvasive small-animal imaging technologies is key to the further development of targeted tracers and therapeutic agents [11,[13][14][15]36].…”

“…The functional imaging capabilities of these noninvasive small-animal imaging devices have been critical to translational drug development [11,14]. In addition to providing the opportunity to quantify functional measures of tumors in vivo, such a noninvasive imaging strategy allows for the opportunity to study the effects of drugs in a longitudinal and serial fashion, yet without the necessity of sacrificing animals to assess the therapeutic response [13][14][15][37][38][39].…”

“…The most readily available, state-of-the-art smallanimal imaging devices provide combined PET, SPECT and CT capabilities [13][14][15][36][37][38][39]. Very recently, combined PET/MRI small-animal scanners have been introduced [30,33].…”

“…This overall effort was designed to facilitate and encourage collaboration between imaging scientists and clinical oncology investigators and cancer centers to encourage the identification and implementation of new oncologic imaging research opportunities in clinical trials and expand the use of targeted imaging biomarkers in clinical therapeutic trials. In this regard, the specific utilization of 18 F-fluorodeoxyglucose PET in clinical trials has proven to have accelerated drug discovery and development [38].…”