Development Of Positron Emission Tomography Probes Research Articles

Recent Advances in Microfluidic Devices for the Radiosynthesis of PET-imaging Probes.

In order to accommodate the growing demand for positron emission tomography (PET), it will be necessary to create innovative radiochemical and engineering technologies to optimize the manufacture and development of PET probes. Microfluidic devices allow radiosynthesis to be performed in microscale amounts, significantly impacting PET tracer production. Compared to traditional methods, microfluidic devices can produce PET tracers in a shorter time, higher yields, with lower reagent consumption, higher molar activity, and faster purification. This review examines microfluidic devices from an engineering perspective. Recently developed microfluidic radiosynthesis devices are classified into three categories according to their reaction volume: continuous-flow, batch-flow, and droplet-based microreactors. The principles of device architecture, radiosynthesis process, and the relative strengths and limitations of each category are emphasized by citing typical examples. Finally, the possible future applications of this technology are outlined. A flexible, miniature, fully automated radiochemical microfluidic platform will offer more straightforward and cheaper molecular imaging procedures and the potential for precision medicine that could allow operators to create customized tracers for individual patient doses.

Recent progress in the imaging of c-Met aberrant cancers with positron emission tomography.

Tyrosine‐protein kinase Met—also known as c‐Met or HGFR—is a membrane receptor protein with associated tyrosine kinase activity physiologically stimulated by its natural ligand, the hepatocyte growth factor (HGF), and is involved in different ways in cancer progression and tumourigenesis. Targeting c‐Met with pharmaceuticals has been preclinically proved to have significant benefits for cancer treatment. Recently, evaluating the protein status during and before c‐Met targeted therapy has been shown of relevant importance by different studies, demonstrating that there is a correlation between the status (e.g., aberrant activation and overexpression) of the HGFR with therapy response and clinical prognosis. Currently, clinical imaging based on positron emission tomography (PET) appears as one of the most promising tools for the in vivo real‐time scanning of irregular alterations of the tyrosine‐protein kinase Met and for the diagnosis of c‐Met related cancers. In this study, we review the recent progress in the imaging of c‐Met aberrant cancers with PET. Particular attention is directed on the development of PET probes with a range of different sizes (HGF, antibodies, anticalines, peptides, and small molecules), and radiolabeled with different radionuclides. The goal of this review is to report all the preclinical imaging studies based on PET imaging reported until now for in vivo diagnosis of c‐Met in oncology to support the design of novel and more effective PET probes for in vivo evaluation of c‐Met.

PET Tracers for Imaging of ABC Transporters at the Blood-Brain Barrier: Principles and Strategies.

ABC transporters at the human blood-brain barrier protect the brain against the entry of harmful compounds but may also limit (or prevent) the cerebral entry of therapeutic drugs (e.g. anti-epileptics, antidepressants and antipsychotics). The efflux function of these transporters may be impaired in neurodegenerative disorders like Alzheimer and Parkinson disease. For such reasons, there is much interest in modulation of the efflux function of ABC transporters and in the monitoring of this function with positron emission tomography (PET). The efflux function of P-glycoprotein, an important member of the ABC transporter family, can be quantified with the PET tracer (R)-[11C]verapamil, but the lipophilicity of this probe and the formation of radioactive metabolites which enter the brain complicate such measurements considerably. (R)-[11C]verapamil is also not very suitable for the detection of P-gp upregulation, as may occur in epilepsy or drug resistance. Current radiochemical efforts are therefore focused on the development of PET probes with improved characteristics, for example; capability to detect both up- and down regulation of transporter function and expression, a better metabolic profile (no brain-entering metabolites), reduced lipophilicity and a longer physical half-life (labeling with 18F instead of 11C).

Microfluidics for Positron Emission Tomography Probe Development

Owing to increased needs for positron emission tomography (PET), high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidics-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates, and easier purification processes with greater yield and higher specific activity of desired probes. Several proof-of-principle examples along with the basics of device architecture and operation and the potential limitations of each design are discussed. Along with the concept of radioisotope distribution from centralized cyclotron facilities to individual imaging centers and laboratories ("decentralized model"), an easy-to-use, stand-alone, flexible, fully automated, radiochemical microfluidic platform can provide simpler and more cost-effective procedures for molecular imaging using PET.