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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.
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.
Structural and Molecular Imaging in Cancer Therapy Clinical Trials
Published in John Crowley, Antje Hoering, Handbook of Statisticsin Clinical Oncology, 2012
Brenda F. Kurland, David A. Mankoff
Currently, the most commonly used PET radiotracer is FDG (18F-fluorodeoxy-glucose), which is a radiolabeled glucose analog and a tracer of glucose metabolism. Tumors have been shown to be highly glycolytic, with a high rate of glycolysis compared to most normal tissues (Warburg, 1956). FDG is transported into cells using the same transport system as glucose, where it undergoes the first committed step of glucose metabolism, namely phosphorylation by hexokinase to FDG-6-phosphate (FDG-6-P). However, FDG-6-P cannot continue on the glycolysis pathway, and thus is “metabolically trapped” in cells with active glucose metabolism. The rate of FDG-6-P (henceforth abbreviated as FDG) accumulation can be measured as a quantitative estimate of the regional glucose metabolic rate through kinetic analysis of dynamic uptake imaging by PET.
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).
Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2016–2019)
Published in Expert Opinion on Therapeutic Patents, 2020
Carlos Roca, Nuria E. Campillo
During the last years there has been an explosion in the field of positron emission tomography (PET) radiotracer for GSK-3 and radiolabeled imaging probes for PET developed based on known GSK-3 inhibitors [22]. Positron emission tomography (PET) radiotracer for GSK-3 could aid many ongoing clinical research efforts to develop GSK-3 targeted therapeutics by indicating the success and extent of engagement by GSK-3 inhibitors in the brain.
Molecular imaging to guide precision diagnosis and prevention of cancer therapeutics-related cardiac dysfunction
Published in Expert Review of Molecular Diagnostics, 2020
Perhaps the most widely used PET radiotracer in clinical practice is 18F-fluorodeoxyglucose (18F-FDG), a glucose analog which is preferentially taken up by metabolically active cells (secondary to upregulation of glycolytic pathways). Whereas 18F-FDG-PET is an established method in the monitoring of cancer patients and their response to treatment, recent studies suggest that myocardial 18F-FDG uptake in the setting of chemotherapy may also serve as a diagnostic marker of cardiotoxicity. In a study of 121 consecutive breast cancer patients undergoing treatment with anthracyclines or trastuzumab, those who developed CTRCD showed higher and more diffuse 18F-FDG uptake in the left ventricle and a greater interval increase in right ventricular 18F-FDG compared to the non-CTRCD group. Of note, the association between 18F-FDG uptake in the right-ventricular wall and CTRCD was found to be independent of age, concomitant radiotherapy and treatment type [6]. Similar findings have been reported in Hodgkin lymphoma patients undergoing doxorubicin-based chemotherapy, as shown in a retrospective analysis of 43 patients which described a significant association between higher left ventricular 18F-FDG uptake at the end of treatment and a greater decrease in LVEF post-chemotherapy compared to the pre-treatment values (R2 = 0.30, P < 0.01) [7]. Pre-clinical studies supplement these reports by providing an insight into additional mechanisms underlying the observed clinical associations. In mouse models of neuroblastoma treated with doxorubicin, myocardial 18F-FDG uptake directly correlated with myocardial redox stress and hexose-6-phosphate-dehydrogenase enzymatic activity, thus supporting the value of 18F-FDG as a potential marker of not only inflammatory activation but also oxidative stress [8]. However, given its physiologic uptake by the myocardium, 18F-FDG may lack the specificity needed to characterize inflammation-specific changes in cardiovascular biology as a result of cancer therapy.