Exploring Geometrical, Electronic and Spectroscopic Properties of 2-Nitroimidazole-Based Radiopharmaceuticals via Computational Chemistry Methods.

Tumor hypoxia plays an important role in the clinical management and treatment planning of various cancers. The use of 2-nitroimidazole-based radiopharmaceuticals has been the most successful for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging probes, offering noninvasive means to assess tumor hypoxia. In this study we performed detailed computational investigations of the most used compounds for PET imaging, focusing on those derived from 2-nitroimidazole: fluoromisonidazole (FMISO), fluoroazomycin arabinoside (FAZA), fluoroetanidazole (FETA), fluoroerythronitroimidazole (FETNIM) and 2-(2-nitroimidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5). Conformational analysis, structural parameters, vibrational IR and Raman properties (within both harmonic and anharmonic approximations), as well as the NMR shielding tensors and spin-spin coupling constants were obtained by density functional theory (DFT) calculations and then correlated with experimental findings, where available. Furthermore, time-dependent DFT computations reveal insight into the excited states of the compounds. Our results predict a significant change in the conformational landscape of most of the investigated compounds when transitioning from the gas phase to aqueous solution. According to computational data, the 2-nitroimidazole moiety determines to a large extent the spectroscopic properties of its derivatives. Due to the limited structural information available in the current literature for the investigated compounds, the findings presented herein deepen the current understanding of the electronic structures of these five radiopharmaceuticals.

Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade.

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [18F]-FDG and NA [18F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of 11C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissues and organs. The radioisotopes typically used in SPECT imaging are iodine-123, technetium-99m, xenon-133, thallium-201, and indium-111. This systematic review article aims to clarify and disseminate the available scientific literature focused on PET/SPECT radiotracers and to provide an overview of the conducted research within the past decade, with an additional focus on the novel radiopharmaceuticals developed for medical imaging.