Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

Complete response to therapy: why do primary central nervous system lymphoma patients not return to work?

Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely...     

Iron overload in congenital haemolytic anaemias: role of hepcidin and cytokines and predictive value of ferritin and transferrin saturation

Iron overload (IO) is poorly investigated in the congenital haemolytic anaemias (CHAs), a heterogeneous group of rare inherited diseases encompassing abnormalities of the erythrocyte membrane and metabolism, and defects of the erythropoiesis. In this study we systematically evaluated routine iron parameters and cardiac and hepatic magnetic resonance imaging, together with erythropoietin, hepcidin, non-transferrin bound iron (NTBI), and cytokine serum levels in patients with different CHAs. We found that 40% of patients had a liver iron concentration (LIC) >4 mg Fe/g dry weight. Hepatic IO was associated with ferritin levels (P = 0·0025), transferrin saturation (TfSat, P = 0·002) and NTBI (P = 0·003). Moreover, ferritin >500 μg/l plus TfSat >60% was demonstrated as the best combination able to identify increased LIC, and TfSat alteration as more important in cases with discordant values. Possible confounding factors, such as transfusions, hepatic disease, metabolic syndrome and hereditary haemochromatosis-associated mutations, had negligible effects on IO. Erythropoietin and hepcidin levels were increased in CHAs compared with controls, correlating with LIC and ferritin, respectively. Regarding cytokines, γ-interferon (IFN-γ) was increased, and both interleukin 6 and IFN-γ levels positively correlated with ferritin and hepcidin levels. Overall, these findings suggest the existence of a vicious cycle between chronic haemolysis, inflammatory response and IO in CHAs.     

What are the preferred characteristics of a service robot for the elderly? A multi-country focus group study with older adults and caregivers

This multi-perspective study focuses on how a service robot for the elderly should behave when interacting with potential users. An existing service robot and a scenario were used as a concrete case, which was discussed and analyzed during focus group sessions with older adults (n = 38), informal caregivers (n = 24), and professional caregivers (n = 35) in the Netherlands, France, and the United Kingdom. A total of seven topics—privacy, task execution, environment, appearance, behavior, visitors, and communication—were explored. The results showed that some of the characteristics mentioned were unique to a user group, but several were cross-cutting. Overall, potential users expected the service robot to be customizable in order to match the users’ needs and preferences. Also, high expectations concerning its functioning and behavior were expressed, which sometimes could even be compared to the qualities of a human being. This emphasizes the complexity of service robot development for older adults, and highlights the need for a personalized and flexible solution. One size does not fit all, and specific attention should be paid to the development of the robot’s social behavior and skills beyond a mere functional support for the person.     

Evaluation of Biodentine in Pulpotomies of Primary Teeth with Different Stages of Root Resorption Using a Novel Composite Outcome Score

This study aimed to assess the success of pulpotomy in primary molars using Biodentine, new-developed tri-calcium, di-calcium-based silicate cement, at 6 and 12 months. The hypothesis was that stages of root resorption could influence the treatment success. A novel composite score was used based on five clinical and radiographic outcomes: soft-tissue pathology, pain to percussion, pathologic mobility, radiolucency and pathologic root resorption. Patients’ compliance and intraoperative pain experience were recorded using the Frankl scale and the Wong–Baker scale. A total of 22 primary molars, 9 in stage S (stability) and 13 in stage R (resorption) were submitted to pulpotomy using Biodentine and restored with composite resin. The success rate was 92.3% in the R group compared to 100% in the S group at both 6 and 12 months (p = 0.850). There was no statistically significant effect of type of molar, tooth position and type of carious lesions on the composite outcome (all p > 0.05). Overall, 73% of the children experienced no or mild/moderate pain and 77% had a cooperative attitude. Children younger than 7 years old experienced more pain (p = 0.04). Biodentine is a promising biomaterial for pulpotomy of primary teeth regardless of the stage of root resorption.     

Prexasertib,a checkpoint kinase inhibitor: from preclinical data to clinical development

Cancer Chemotherapy and Pharmacology - Checkpoint kinases 1 and 2 (CHK1 and CHK2) are important multifunctional proteins of the kinase family. Their main function is to regulate DNA replication and...     

Neural coding of action in three dimensions: Task- and time-invariant reference frames for visuospatial and motor-related activity in parietal area V6A

Goal-directed movements involve a series of neural computations that compare the sensory representations of goal location and effector position, and transform these into motor commands. Neurons in posterior parietal cortex (PPC) control several effectors (e.g., eye, hand, foot) and encode goal location in a variety of spatial coordinate systems, including those anchored to gaze direction, and to the positions of the head, shoulder, or hand. However, there is little evidence on whether reference frames depend also on the effector and/or type of motor response. We addressed this issue in macaque PPC area V6A, where previous reports using a fixate-to-reach in depth task, from different starting arm positions, indicated that most units use mixed body/hand-centered coordinates. Here, we applied singular value decomposition and gradient analyses to characterize the reference frames in V6A while the animals, instead of arm reaching, performed a nonspatial motor response (hand lift). We found that most neurons used mixed body/hand coordinates, instead of “pure” body-, or hand-centered coordinates. During the task progress the effect of hand position on activity became stronger compared to target location. Activity consistent with body-centered coding was present only in a subset of neurons active early in the task. Applying the same analyses to a population of V6A neurons recorded during the fixate-to-reach task yielded similar results. These findings suggest that V6A neurons use consistent reference frames between spatial and nonspatial motor responses, a functional property that may allow the integration of spatial awareness and movement control.