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Antibody-based Radionuclide Imaging
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Steffie M.B. Peters, Erik H. J. G. Aarntzen, Sandra Heskamp
Evidently, when using radionuclides for imaging, the patient will be exposed to radiation. However, the final effective dose that the patient receives depends on many different factors. Each radionuclide disposes a different dose per injected activity, dependent on type of radiation and emission energy. The total amount of injected activity is furthermore determined by the imaging characteristics of the radionuclide. The amount of activity should be sufficient for imaging with an acceptable signal-to-noise ratio at the relevant timepoint. The mAb that the radionuclide is coupled to, mainly determines the location in the body at which the radionuclide will deliver its radiation and, thereby, which organs and structures are mainly affected by the radiation. As an example, imaging using the PET radiotracer 89Zr with a typical injected activity of ±37 MBq leads to an effective dose to the patient of around 22 mSv. Although it might seem counterintuitive, using the SPECT radiotracer 111In typically leads to the same effective dose of 22 mSv to the patient, despite the lower dose-conversion factor. This is due to the fact that a higher injected activity is required (~100MBq) due to the lower sensitivity of the SPECT scanner.
Medical and Biological Applications of Low Energy Accelerators
Published in Vlado Valković, Low Energy Particle Accelerator-Based Technologies and Their Applications, 2022
PET is a diagnostic imaging procedure used regularly to acquire essential clinical information. The PET-CT hybrid, which consists of two scanning machines: PET scanner and an X-ray CT. At present, these represent the technological hierarchy of Nuclear Medicine, occupying an important position in diagnostics. In fact, PET-CT has the capability to evaluate diseases through a simultaneous functional and morphostructural analysis. This allows for an earlier diagnosis of the disease state, which is crucial for obtaining the required information to provide a more reliable prognosis and therapy. Presently, the most frequently used PET radiotracer fluorodeoxyglucose (18FDG) has a major role in oncology. Useful information is being regularly obtained by using both 18FDG and a selection of radiotracer compounds to evaluate some of the most important biological processes (Kitson et al. 2009).
Positron Emission Tomography
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
A positron emission tomography (PET) scanner is designed to provide a measurement of the spatial distribution of a PET radiotracer within a subject. Measurements can be made in a time series to provide a “movie” showing quantitatively how this distribution changes over time. Such change is related to the underlying biology under investigation. PET uses the tracer principle: a compound is tagged with a radionuclide and a small (trace) amount is injected. Because it is a trace amount, it does not affect the biological system in any way (e.g., no saturation of binding sites and no clinical effects), thus allowing the measurement of the system in its natural state. Many of the PET radionuclides are isotopes of elements naturally present in the body (carbon, oxygen, etc.), thus allowing for their easy incorporation into biologically relevant compounds. The ultimate results of positron emission are two high-energy annihilation photons. These high-energy (511 keV) photons can easily penetrate through the body of the animal with minimal interactions and can be detected in coincidence. This chapter describes the physics of PET together with a short overview of data quantification and reconstruction and data analysis and interpretation.
Findings from Positron Emission Tomography-Computed Tomography with 18F-Fluorodeoxyglucose Uncover a Potential Marker of Nutritional Status in Cancer Patients: A Cross-Sectional Pilot Study
Published in Nutrition and Cancer, 2023
Bernardo Faria Levindo Coelho, Thales Antonio da Silva, Álida Rosária Silva Ferreira, Leonardo Lamego Resende, Luciana Costa-Silva, Maria Isabel Toulson Davisson Correia
Patients with cancer periodically undergo clinical and imaging follow-up, and PET/CT is routinely used in the evaluation of several neoplasms, providing anatomical and metabolic information using radiotracers (1–5). The most frequently used PET radiotracer is 18F-fluorodeoxyglucose (18F-FDG) (6). Several tumors consume glucose, and their glycolytic metabolism allows the generation of functional images for the locoregional and systemic assessment of the disease (7, 8). The principle that justifies the use of 18F-FDG is based on the increase in glucose metabolism by tumor cells. Analogous to glucose, 18F-FDG is taken up by the cells via glucose transporters (GLUT). Hepatocytes also express GLUT 2, GLUT 9 and GLUT 10, making the liver an important organ for glucose and analogue metabolism. The hepatic SUVmean corresponds to the mean uptake of 18F-FDG in regions of normal liver parenchyma. As the liver parenchyma is rich in glucose-6-phosphatase, there is rapid and stable clearance of 18F-FDG in this organ. Thus, specifically considering this stability of hepatic glucose and analogue metabolism, the mean intensity of hepatic 18F-FDG uptake has often been used in clinical practice as a reference for evaluating uptake in other organs and regions suspected of neoplastic involvement (8).
Synthetic methodologies and PET imaging applications of fluorine-18 radiotracers: a patent review
Published in Expert Opinion on Therapeutic Patents, 2022
Sridhar Goud Nerella, Ahana Bhattacharya, Pavitra S Thacker, Sanam Tulja
The remarkable 18F-radiotracer that has been widely used in clinical applications for three decades is [18F]FDG and regarded as a potential positron emission tomography (PET) imaging agent to detect various conditions in oncology, cardiology, and neurology [5]. Recently, the patent WO 2017/203,017 also reported a specific and rare application of [18F]FDG that it can also be labeled with Red Blood Cells to measure blood pool in living subjects, where it is briefly explained that how it reveals more clinical information through PET [6]. Various 18F-radiotracers are currently used for PET imaging studies in different conditions due to many advantages with fluorine-18 in comparison with other PET radionuclides [7]. It is considered as an ideal radionuclide for PET radiotracer development because the half-life of fluorine-18 is 109.8 min, which is higher than other positron emitting radionuclides. Fluorine-18 is well tolerated for long-run radiosynthesis, and easily accessible for transportation to different clinical PET centers and research institutions because the establishment of cyclotron facility is associated with high cost and maintenance; therefore, 18F-radiotracers fulfill the needs of biomedical researchers and clinicians for PET imaging studies with a longer half-life. Several industries are developing cGMP compliance 18F-radiopharmaceuticals in a cyclotron-based commercial site and distributing them near PET clinical centers [8].
An updated patent review on P-glycoprotein inhibitors (2011-2018)
Published in Expert Opinion on Therapeutic Patents, 2019
Marcello Leopoldo, Patrizia Nardulli, Marialessandra Contino, Francesco Leonetti, Gert Luurtsema, Nicola Antonio Colabufo
Verapamil (Figure 1(b)) is a calcium channel blocker and classified as P-gp substrate and is used as PET radiotracer (11C-verapamil) alone and in coadministration with P-gp inhibitors such as tariquidar (Figure 1(a)), to study the radiotracer uptake, alone and in the presence of inhibitor, both in in vitro (cell monolayer) and in vivo animal model (rodens in PET studies) [6,7]. On the other hand, several studies reported that verapamil or desmethylloperamide (Figure 1(b)) reverted the multidrug resistance in tumor cells overexpressing P-gp rehabilitating the proper chemotherapeutic drug concentration into the cells. The question arises if verapamil and desmethylloperamide are substrates or inhibitors toward the transporter? A reasonable compromise could be that P-gp has different binding sites, for substrates (i.e. verapamil), modulators (i.e. cyclosporine, Figure 1(c)), and inhibitors (i.e. tariquidar). Therefore, the binding sites display different site- and dose-depending kinetic profile [8]. This observation could support the verapamil activity both as substrate and inhibitor. The turnover of verapamil on the substrate site is elevated but high concentration can saturate the pump activity leading, as final effect, to a P-gp inhibitory action. When verapamil is used as radiotracer, at low concentration, it displays a ‘pure’ P-gp substrate behavior. Demethylloperamide is a potent substrate because, loperamide is P-g substrate but, the in vivo metabolite, demthetyloperamide, is a very potent P-gp substrate. For his reason it is extensively employed as P-gp substrate with respect to verapamil because verapamil displays t1/2 comparable with loperamide but verapamil t1/2 is ≪ of desmethylloperamide.