scholarly journals Investigation of Fluorine-18 Labelled Peptides for Binding to Cholecystokinin-2 Receptors with High Affinity

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Naeem-Ul-Haq Khan ◽  
Alicia Corlett ◽  
Craig A. Hutton ◽  
Mohammad B. Haskali
Keyword(s):  
Medullary Thyroid Cancer ◽  
Positron Emission Tomography Imaging ◽  
Radiochemical Yield ◽  
Binding Assays ◽  
A431 Cells ◽  
Activated Esters ◽  
Chemically Modified ◽  
Positron Emission ◽  
The Impact

AbstractMany cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other lung carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization and quantification of this receptor in vivo using positron emission tomography imaging. CP04 1 and MG11 2 are two previously described truncated peptides derived from the native CCK-2R hormone ligand, gastrin. The N-terminus of the MG11 2 octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) and aliphatic (2-fluoropropionate) moieties. To assess the impact these modifications had on CCK-2R binding, ligand-binding assays were conducted using A431 cells overexpressing human CCK-2R. MG11 2 modified by 4-fluorobenzoate (FB-MG11 3) demonstrated the highest binding affinity (0.20 nM) followed by MG11 2 modified by 6-fluoronicotinate (FNic-MG11 4; 0.74 nM) and 2-fluoropropionate (FP-MG11 5; 1.80 nM), respectively. Whilst indirect labelling of MG11 2 using fluorine-18 labelled activated esters of fluorobenzoate and 6-fluoronicotinate was unsuccessful, direct fluorine-18 labelling at the N-terminus modified with 6-nitronicotinate afforded a 47.6% radiochemical yield of [18F]FNic-MG11. Unfortunately, [18F]FNic-MG11 4 was chemically unstable, decomposing slowly through defluorination, thereby impeding any further work with this radiotracer.

Click Chemistry Expedited Radiosynthesis: Sulfur [18F]fluoride Exchange of Aryl Fluorosulfates

2019 ◽  
Author(s):  
Qinheng Zheng ◽  
Hongtao Xu ◽  
Hua Wang ◽  
Wen-Ge Han Du ◽  
Nan Wang ◽  
...  
Keyword(s):  
Click Chemistry ◽  
High Performance ◽  
Isotopic Exchange ◽  
Tumor Imaging ◽  
Radiochemical Yield ◽  
Exchange Method ◽  
Molar Activity ◽  
Positron Emission ◽  
Sulfur Fluoride

The lack of simple, efficient [<sup>18</sup>F]fluorination processes and new target-specific organofluorine probes remains the major challenge of fluorine-18-based positron emission tomography (PET). We report here a fast isotopic exchange method for the radiosynthesis of aryl [<sup>18</sup>F]fluorosulfate based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully-automated <sup>18</sup>F-radiolabeling of twenty-five structurally diverse aryl fluorosulfates with excellent radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol<sup>–1</sup>) at room temperature in 30 seconds. The purification of radiotracers requires no time-consuming high-performance liquid chromatography (HPLC), but rather a simple cartridge filtration. The utility of aryl [<sup>18</sup>F]fluorosulfate is demonstrated by the <i>in vivo</i> tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).

scholarly journals Development of 2-Deoxy-2-[18F]fluororibose for Positron Emission Tomography Imaging Liver Function in Vivo

2015 ◽  
Vol 58 (14) ◽  
pp. 5538-5547 ◽  
Author(s):  
Nikolai M. Evdokimov ◽  
Peter M. Clark ◽  
Graciela Flores ◽  
Timothy Chai ◽  
Kym F. Faull ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Liver Function ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Tomography Imaging ◽  
Positron Emission

scholarly journals Effect of Insulin and Dexamethasone on Fetal Assimilation of Maternal Glucose

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 255-262 ◽  
Author(s):  
Andrew W. Norris ◽  
Chunlin Wang ◽  
Jianrong Yao ◽  
Susan A. Walsh ◽  
Alexander B. Sawatzke ◽  
...  
Keyword(s):  
Positron Emission Tomography Imaging ◽  
Maternal Blood ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Positron Emission ◽  
Brown Adipose ◽  
Maternal Brain ◽  
D 20 ◽  
Fdg Accumulation ◽  
Maternal Glucose

Abstract The growing fetus depends upon transfer of glucose from maternal blood to fetal tissues. Insulin and glucocorticoid impact maternal glucose metabolism, but the effects of these hormones on fetal glucose assimilation in vivo are understudied. We thus used positron emission tomography imaging to determine the disposition of [18F]fluorodeoxyglucose (FDG) in rats on gestational d 20, quantifying the kinetic competition of maternal tissues and fetus for glucose. Three fasting maternal states were studied: after 2-d dexamethasone (DEX), during euglycemic hyperinsulinemic clamp insulin receiving (INS), and control (CON). In CON and DEX mothers, FDG accumulation in fetuses and placentae was substantial, rivaling that of maternal brain. By contrast, FDG accumulation was reduced in INS fetuses, placentae, and maternal brain by approximately 2-fold, despite no diminution in FDG extraction kinetics from maternal blood into these structures. The reduced FDG accumulation was due to more rapid clearance of FDG from the circulation in INS mothers, related to increased FDG avidity in INS select maternal tissues, including skeletal muscle, brown adipose tissue, and heart. DEX treatment of mothers reduced fetal weight by nearly 10%. Nonetheless, the accumulation of FDG into placentae and fetuses was similar in DEX and CON mothers. In our rat model, fetal growth restriction induced by DEX does not involve diminished glucose transport to the fetus. Maternal insulin action has little effect on the inherent avidity of the fetal-placental unit for glucose but increases glucose utilization by maternal tissues, thus indirectly reducing the glucose available to the fetus.

scholarly journals Repeated social defeat induces transient glial activation and brain hypometabolism: A positron emission tomography imaging study

2017 ◽  
Vol 39 (3) ◽  
pp. 439-453 ◽  
Author(s):  
Paula Kopschina Feltes ◽  
Erik FJ de Vries ◽  
Luis E Juarez-Orozco ◽  
Ewelina Kurtys ◽  
Rudi AJO Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Positron Emission Tomography Imaging ◽  
Imaging Study ◽  
Social Defeat ◽  
Glial Activation ◽  
Emission Tomography ◽  
Biochemical Alterations ◽  
Positron Emission

Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short- and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats ( n = 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation (11C-PK11195 PET) and changes in brain metabolism (18F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive- and anxiety-like behaviour, increased corticosterone and brain IL-1β levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third- and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.

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