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Imaging Dopamine Signaling in Addiction
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Diana Martinez, Felipe Castillo
The main outcome measure used in PET and SPECT imaging studies of clinical populations is called “binding potential” (BP). Binding potential is obtained from the ratio of specific binding to nonspecific binding. This is illustrated in Figure 30.1, where specific binding refers to the radiotracer bound to the receptor or cellular target of interest, while nonspecific binding is the radiotracer bound to other non-target proteins in the brain. Nonspecific binding is generally low, and using this ratio as an outcome measure provides a method for normalizing the signal across subjects and across conditions.
Cardiovascular PET-CT
Published in Yi-Hwa Liu, Albert J. Sinusas, Hybrid Imaging in Cardiovascular Medicine, 2017
Etienne Croteau, Ran Klein, Jennifer M. Renaud, Manuja Premaratne, Robert A. Dekemp
From the reconstructed tomographic images, the spatial and temporal distributions of the radiotracer in the organ of interest are obtained. With the appropriate corrections, calibration, and knowledge of the specific activity (GBq/mmol) of the administered tracer, the isotope activity or tracer molar concentration per unit of tissue volume (Bq/cc or mmol/L) can be assessed quantitatively. Semiquantitative biodistribution analysis can also be performed, where the activity concentration is normalized by the total amount of activity injected and the subject body weight to determine the standard uptake value in g/cc or g/mL. Additionally, dynamic PET imaging can be used to assess in vivo physiology, biochemistry, or receptor binding of a tracer by quantifying properties such as organ perfusion (mL/min/g), substrate metabolism (mol/min/g), receptor density (pmol/cc), or receptor-ligand binding potential (Bmax/Kd) (Beauregard et al. 2007).
Novel imaging techniques
Published in Harald Breivik, William I Campbell, Michael K Nicholas, Clinical Pain Management, 2008
Early opioid ligand studies showed decreased binding in chronic pain patients that normalized after reduction of their pain symptoms.26 Regional differences in ligand binding within key pain processing brain regions have also been reported in several neuropathic pain studies.27,28 A study of restless legs syndrome found that the opioid-binding potential is negatively correlated with the affective dimension of the McGill Pain Questionnaire.29 A recent study by Maarrawi and colleagues30 demonstrates differential brain opioid receptor availability between patients with central and peripheral neuropathic pain. They found a bilateral binding decrease in both patient groups that could reflect endogenous opioid release secondary to their chronic pain, but they also found a more significant and lateralized decrease specific to the central poststroke pain patients, suggestive of opioid receptor loss or inactivation in receptor-bearing neurons. This binding decrease was more extensive than the brain anatomical lesions and not colocalized to them. These findings have important implications because if central and peripheral forms of neuropathic pain differ in the distribution of opioid system changes, this might account for a differential sensitivity to opiates. For all these studies, causation is an issue. Future studies, in particular longitudinal studies that correlate binding potential with pain intensity, are needed to help elucidate whether decreased receptor availability is caused by increased release of endogenous opioids or decreased receptor density.
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 Positron Emission Tomography (PET) imaging modality visualizes and measures physiological processes at the molecular level, such as measurement of receptor density, glucose metabolism, neurotransmitters, uptakes, blood flow, and so on in oncology, cardiology, and various neurological conditions [1]. PET is an essential molecular imaging tool that helps biomedical researchers and clinicians to study functional physiological processes of living subjects either in preclinical or clinical studies [2]. It plays a pivotal role in the early stage of the drug discovery process by providing useful knowledge on pharmacokinetic profiles like distribution, metabolism of new drugs, specific target binding, receptor occupancy, receptor-binding potential, and determine therapeutic dosing regimens; therefore, it can enhance the process of clinical trials with more reliable data and estimate changes in therapy and monitor it [3]. The PET becomes a more popular modality for early diagnosis, and it requires a very low concentration of radiotracers in the nM range with negative to very minimal radiation exposure and no pharmacological actions of given radiotracers due to lower concentration than ED50 values. PET provides functional images with limited anatomical information; hence, many advanced technologies have come forward to overcome this limitation by combining PET with other molecular imaging modalities and have emerged as multimodality devices like PET-CT and PET-MRI [4].
A new mixed-ligand coordination polymer: protective activity on influenza a virus-induced COPD via regulating tlr3 gene expression on alveolar epithelial cells
Published in Drug Development and Industrial Pharmacy, 2021
Youhui Tu, Chao Yang, Xiangwei Zhang
Molecular docking method is a tool to help us reflect how the interaction between ligands and receptor proteins preforms at molecular level. Considering the complicated structure of the compound, we truncated the compound and only reserved the functional side chain. As shown in Figure 7, top 4 binding modes were generated with the lowest binding energy, which describes a outline view of the complex offered via the target protein wrapped in a binding bag. Interestingly, four potential binding modes revealed two possible binding sites. The pose 1 (Figure 7(A)) and pose 2 (Figure 7(B)) exhibited similar binding sites with energy contribution of −7.61 and −7.42 kcal/mol, respectively, indicating large possibility for the ligand to bind. While the pose 3 and pose 4 showed a binding potential in another binding site with energy contribution of −5.17 and −5.02 kcal/mol, respectively. Although different binding pockets were observed, the ligand of all the binding modes showed a similar binding patter: the functional sidechain of the carboxyl formed multiple polar interaction, which contributed most binding energy. Thus, the above evidence demonstrated the ligand could recognize the specific sites on TLR3, showing as a rational recognizing group.
Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model
Published in Xenobiotica, 2020
Khalid M. Alkharfy, Fahad A. Ali, Mohammad A. Alkharfy, Basit L. Jan, Mohammad Raish, Saeed Alqahtani, Ajaz Ahmad
The current study explored for the first time, according to our best knowledge, the influence of compromised hepatic and renal functions on the pharmacokinetics of TQ employing animal models of liver dysfunction and acute kidney injury. The impaired kidney and hepatic functions in the current study was evident by the significantly higher levels of kidney and hepatic systemic biomarkers (i.e., Scr and ALT). The pharmacokinetic data of the normal control rats showed that TQ is rapidly eliminated from the body. The interesting reflection that was seen in the concentration time profile of the IV dosing was the bi-phasic decay of TQ. The early quick decline denotes a rapid drug distribution phase as a consequent binding to both plasma and tissue proteins. A protein binding potential of drug in blood plasma is a very important factor affecting its free concentration in the distribution of blood and tissue (Talbi et al., 2014). TQ has a high degree of protein binding to rat plasma (over 99%), significantly reducing free exposure to the compound. This conversely was accompanied by a relatively small volume of distribution, which can be explained by the high drug binding of TQ to plasma proteins due to its poor water solubility (log P value = 2.55).