Single radio UHPLC analysis for the quality control of technetium-99m radiolabelled radiopharmaceuticals.

The radiochemical purity (RCP) determination of radiopharmaceuticals is routinely done with radio-thin layer chromatography (r-TLC). These methods are usually transposed and adjusted from the summary product characteristics without any analytical validation. The r-TLC method is simple but manually-performed steps could lead to RCP misinterpretation. To increase the sensitivity, radio ultra-high performance liquid chromatography (r-UHPLC) can be used. In this study, an r-UHPLC method had been validated and compared to the r-TLC method. Hydrolyzed-reduced technetium had also been studied.

PET and SPECT Radiotracers for Alzheimer's Disease.

The two main pathological hallmarks of Alzheimer's disease (AD) in the brain are senile plaques (SPs) composed of beta-amyloid (Aß) peptides and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. These hallmarks are associated with a cholinergic deficit. While the process leading to the development of AD is complex and multifactorial, and the etiology of AD is not completely known, it is nowadays clear that AD is a multifaceted illness requiring the combination of synergetic treatment strategies. Because definite diagnosis is achieved by postmortem examination of the brain, new noninvasive diagnostic imaging modalities for AD are in high demand, both to detect and monitor the evolution of this sickness, and evaluate the efficacy of treatments. Positron Emission Tomography (PET) is a nuclear molecular imaging technique that uses radiopharmaceuticals labeled with a positron-emitting isotope (carbon-11, fluorine-18, copper-64, gallium- 68…), to visualize in vivo cellular metabolism with high-spatial resolution and unique sensitivity, while Single-Photon Emission Computed Tomography (SPECT) using radioisotopes such as technetium-99m or iodine-123. Besides being a powerful tool for diagnosis (mostly in oncology with [(18)F]-FDG), PET experiments can provide information about biochemical mechanisms in living tissues or interactions between neurotransmitter and brain receptors. For the past two decades, numerous radiopharmaceuticals have been developed for imaging the lesions observed in AD patients. Tau aggregates and Aß plaques can also be visualized and quantified by mean of specific radioligands. The latter has been the focus of intense research efforts lately, leading to new FDA approved radiopharmaceuticals. This paper aimed at summarizing the recent advances in PET and SPECT imaging of AD pathophysiology.

Radiosynthesis and in vivo evaluation of fluorinated huprine derivates as PET radiotracers of acetylcholinesterase.

INTRODUCTION: Developing positron emission tomography (PET) radiotracers for non-invasive study of the cholinergic system is crucial to the understanding of neurodegenerative diseases. Although several acetylcholinesterase (AChE) PET tracers radiolabeled with carbon-11 exist, no fluorinated radiotracer is currently used in clinical imaging studies. The purpose of the present study is to describe the first fluorinated PET radiotracer for this brain enzyme. METHODS: Three structural analogs of huprine, a specific AChE inhibitor presenting high affinity towards AChE in vitro, were synthesized and labeled with fluorine-18 via a mesylate/fluoro-nucleophilic aliphatic substitution: ([(18)F]-FHUa, [(18)F]-FHUb and [(18)F]-FHUc). Initial biological evaluation included in vitro autoradiography in rat with competition with an AChE inhibitor at different concentrations, and microPET-scan on anesthetized rats. In vivo PET studies in anesthetized cat focused on [(18)F]-FHUa. RESULTS AND CONCLUSIONS: Although radiosynthesis of these huprine analogs was straightforward, they showed poor brain penetration potential, partially reversed after pharmacological inhibition of P-glycoprotein. These results indicated that current huprine analogs are not suitable for PET mapping of brain AChE receptors, but require physicochemical modulation in order to increase brain penetration.