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.     

Expression of ER,PgR, HER-2, and Ki-67 in core biopsies and in definitive histological specimens in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy

Cancer Chemotherapy and Pharmacology - Many studies have indicated that the response to therapy and the prognostic impact of a pathologic complete response after neoadjuvant treatment differ among...     

Validation of the Italian version of the Kagan scales for people with aphasia and their conversation partners

Background: The importance of conversation partners (CPs) for persons with aphasia (PwA) was recently highlighted. Trained CPs are shown to increase communicative access and improve quality of life. The Kagan scales, i.e., “Measure of skills in Supported Conversation” and “Measure of Participation in Conversation” (the MSC-MPC scales), between PwA and their CPs were designed to assess the communication dyad. The MSC-MPC scales were translated and adapted to Italian in 2015.

Aim: To validate the Italian version of the MSC-MPC scales (I-MSC/MPC) by assessing intra- and inter-rater reliability and concurrent validity.

Methods & Procedures: Thirty-two couples formed by 16 PwA and two CPs (one trained and one untrained) for each PwA were enrolled in the study. Aphasia severity was staged by the Therapy Outcome Measures “Dysphasia” impairment scale. Functional communication and pragmatic abilities were assessed with the I-ASHA-FACS and the Pragmatic Protocol, respectively. The PwA were videotaped while communicating both with trained and untrained CPs. All videotapes were assessed using the I-MSC/MPC scales by one expert speech and language therapist and two trainee speech and language therapists. The Intraclass Correlation Coefficient (ICC) was used to calculate inter- and intra-rater reliability. Correlations between the I-MSC/MPC scales and the aphasia severity, the I-ASHA-FACS, and the Pragmatic Protocol results were calculated by the Spearman’s test. The Mann-Whitney test was used to separate the I-MSC/MPC results obtained by the trained CPs from the untrained CPs.

Outcomes & Results: Inter-rater and intra-rater reliability ICC results were highly significant and strong (ICC > .906, ICC > .978, p < .001, respectively). Significant correlations between the aphasia severity and the I-MSC/MPC scales ranged from moderate to strong (Spearman rho>.487, p < .005). Correlations between the I-MSC and the I-ASHA-FACS domains ranged from moderate to strong (rho >.458, p < .008). Correlation between the I-MPC and the I-ASHA-FACS domains were generally strong (rho > .569, p < .001) while correlations between the I-MSC and the I-ASHA-FACS domains ranged from moderate to strong (rho > .458, p = .008). Pragmatic aspects were shown to be mostly preserved in the PwA. All correlations between the I-MSC/MPC scales and the Pragmatic Protocol were strong (rho >.635, p < .008). The Mann-Whitney test showed significant results for the I-MSC scale (p < .026).

Conclusions: The I-MSC-MPC scales proved to be a valid and reliable instrument to assess the communicative dyad. The I-MSC scale was also used to distinguish trained from untrained CPs. The use of I-MSC-MPC scales is recommended in clinical practice.     

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.     

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.     

Fetal pancreatic Langerhans islets size in pregnancies with metabolic disorders

Objective: Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short- and long-term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected.

Aim: To investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses.

Methods: Samples from fetal pancreas underwent a quantitative histological evaluation to detect differences between pregnancy with (cases, n?=?9) or without (controls, n?=?6) abnormal metabolism.

Results: Results show that the islets size increases in fetuses from dysmetabolic pregnancies and that this increment is related to both beta-cell hyperplasia and hypertrophy. Moreover, according to pregnancy and fetal metabolic disorders, a threshold of abnormal size of the islets has been identified. Above this threshold the size of fetal pancreatic Langerhans islets should be considered excessively increased.

Conclusion: The study suggests that an accurate fetal pancreas analysis supplies an important tool in stillborn fetus, to discover metabolic disturbances that should be kept in mind and managed in future pregnancies.