scholarly journals Anti-Human PD-L1 Nanobody for Immuno-PET Imaging: Validation of a Conjugation Strategy for Clinical Translation

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1388 ◽  
Author(s):  
Jessica Bridoux ◽  
Katrijn Broos ◽  
Quentin Lecocq ◽  
Pieterjan Debie ◽  
Charlotte Martin ◽  
...  
Keyword(s):  
Cell Function ◽  
Positron Emission Tomography Imaging ◽  
Clinical Translation ◽  
Immune Checkpoints ◽  
Positron Emission ◽  
Specific Tumor ◽  
Programmed Death ◽  
High Yields ◽  
Organ Targeting

Immune checkpoints, such as programmed death-ligand 1 (PD-L1), limit T-cell function and tumor cells use this ligand to escape the anti-tumor immune response. Treatments with monoclonal antibodies blocking these checkpoints have shown long-lasting responses, but only in a subset of patients. This study aims to develop a Nanobody (Nb)-based probe in order to assess human PD-L1 (hPD-L1) expression using positron emission tomography imaging, and to compare the influence of two different radiolabeling strategies, since the Nb has a lysine in its complementarity determining region (CDR), which may impact its affinity upon functionalization. The Nb has been conjugated with the NOTA chelator site-specifically via the Sortase-A enzyme or randomly on its lysines. [68Ga]Ga-NOTA-(hPD-L1) Nbs were obtained in >95% radiochemical purity. In vivo tumor targeting studies at 1 h 20 post-injection revealed specific tumor uptake of 1.89 ± 0.40%IA/g for the site-specific conjugate, 1.77 ± 0.29%IA/g for the random conjugate, no nonspecific organ targeting, and excretion via the kidneys and bladder. Both strategies allowed for easily obtaining 68Ga-labeled hPD-L1 Nbs in high yields. The two conjugates were stable and showed excellent in vivo targeting. Moreover, we proved that the random lysine-conjugation is a valid strategy for clinical translation of the hPD-L1 Nb, despite the lysine present in the CDR.

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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