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Radiolabeled peptides have been the subject of intense research efforts for targeted diagnostic imaging and radiotherapy over the last 20 years. Peptides offer several advantages for receptor imaging and targeted radiotherapy. The low molecular weight of peptides allows for rapid clearance from the blood and non-target tissue, which results in favorable target-to-non-target ratios. Moreover, peptides usually display good tissue penetration and they are generally non-immunogenic. A major drawback is their potential low metabolic stability. The majority of currently used radiolabeled peptides for targeted molecular imaging and therapy of cancer is labeled with various radiometals like 99mTc, 68Ga, and 177Lu. However, over the last decade an increasing number of 18F-labeled peptides have been reported. Despite of obvious advantages of 18F like its ease of production in large quantities at high specific activity, the low β+ energy (0.64 MeV) and the favorable half-life (109.8 min), 18F-labeling of peptides remains a special challenge. The first part of this review will provide a brief overview on chemical strategies for peptide labeling with 18F. A second part will discuss recent technological advances for 18F-labeling of peptides with special focus on microfluidic technology, automation, and kit-like preparation of 18F-labeled peptides. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a preclinical and clinical imaging technique extensively used to study and visualize biological and physiological processes in vivo. Fluorine-18 (18F) is the most frequently used positron emitter for PET imaging due to its convenient 109.8 min half-life, high yield production on small biomedical cyclotrons, and well-established radiofluorination chemistry. The presence of fluorine atoms in many drugs opens new possibilities for developing radioligands labelled with fluorine-18. The trifluoromethyl group (CF3) represents a versatile structural motif in medicinal and pharmaceutical chemistry to design and synthesize drug molecules with favourable pharmacological properties. This fact also makes CF3 groups an exciting synthesis target from a PET tracer discovery perspective. Early attempts to synthesize [18F]CF3-containing radiotracers were mainly hampered by low radiochemical yields and additional challenges such as low radiochemical purity and molar activity. However, recent innovations in [18F]trifluoromethylation chemistry have significantly expanded the chemical toolbox to synthesize fluorine-18-labelled radiotracers. This review presents the development of significant [18F]trifluoromethylation chemistry strategies to apply [18F]CF3-containing radiotracers in preclinical and clinical PET imaging studies. The continuous growth of PET as a crucial functional imaging technique in biomedical and clinical research and the increasing number of CF3-containing drugs will be the primary drivers for developing novel [18F]trifluoromethylation chemistry strategies in the future. [ABSTRACT FROM AUTHOR]

Molecular imaging probes enable the early and accurate detection of disease-specific biomarkers and facilitate personalized treatment of many chronic diseases, including cancer. Among current clinically used functional imaging modalities, positron emission tomography (PET) plays a significant role in cancer detection and in monitoring the response to therapeutic interventions. Several preclinical and clinical studies have demonstrated the crucial involvement of cyclooxygenase-2 (COX-2) isozyme in cancer development and progression, making COX-2 a promising cancer biomarker. A variety of COX-2-targeting PET radioligands has been developed based on anti-inflammatory drugs and selective COX-2 inhibitors. However, many of those suffer from non-specific binding and insufficient metabolic stability. This article highlights examples of COX-2-targeting PET radioligands labelled with the short-lived positron emitter 18F, including radiosynthesis and PET imaging studies published in the last decade (2012–2021). [ABSTRACT FROM AUTHOR]

Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[18F]FDF) targets the fructose-preferred facilitative hexose transporter GLUT5, which is expressed predominantly in brain microglia and activated in response to inflammatory stimuli. We hypothesize that 6-[18F]FDF will specifically image microglia following neuroinflammatory insult. 6-[18F]FDF and, for comparison, [18F]FDG were evaluated in unilateral intra-striatal lipopolysaccharide (LPS)-injected male and female rats (50 µg/animal) by longitudinal dynamic PET imaging in vivo. In LPS-injected rats, increased accumulation of 6-[18F]FDF was observed at 48 h post-LPS injection, with plateaued uptake (60–120 min) that was significantly higher in the ipsilateral vs. contralateral striatum (0.985 ± 0.047 and 0.819 ± 0.033 SUV, respectively; p = 0.002, n = 4M/3F). The ipsilateral–contralateral difference in striatal 6-[18F]FDF uptake expressed as binding potential (BPSRTM) peaked at 48 h (0.19 ± 0.11) and was significantly decreased at one and two weeks. In contrast, increased [18F]FDG uptake in the ipsilateral striatum was highest at one week post-LPS injection (BPSRTM = 0.25 ± 0.06, n = 4M). Iba-1 and GFAP immunohistochemistry confirmed LPS-induced activation of microglia and astrocytes, respectively, in ipsilateral striatum. This proof-of-concept study revealed an early response of 6-[18F]FDF to neuroinflammatory stimuli in rat brain. 6-[18F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g. 11C: 20.4 min; 18F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (124I, t1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of 124I as promising PET radionuclide for molecular imaging. The first part describes the production of 124I. The second part covers basic radiochemistry with 124I focused on the synthesis of 124I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter 124I in the field of organic PET chemistry and molecular imaging. [ABSTRACT FROM AUTHOR]