Development of an automated production process of [64Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [⁶⁴Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [⁶⁴Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [⁶⁴Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [⁶⁴Cu][Cu (ATSM)] was 2.2–5.5 Ci/μmol (HPLC), 2.2–2.6 Ci/μmol (ATSM-titration), and 3.0–4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [⁶⁴Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies.     

Prevalence of EBV infection in 1157 diseased cohorts in Nigeria: A systematic review and meta-analysis

BackgroundEpstein-Barr virus (EBV) is a member of the herpesvirus family that is known to ubiquitously infect people worldwide. However, the actual prevalence of EBV infection in diseased patients in Nigeria, remains unknown. This study was thus conducted to ascertain the true prevalence.MethodsA systematic review and meta-analysis of published data was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched for studies reporting the occurrence of EBV infection among patients with established diseases. Studies were included if they assessed EBV infection in diseased patients in Nigeria. Data were extracted and subsequently analysed using R software. Funnel plot and Egger's regression test was used to assess publication bias, while JBI prevalence tool was used to assess study quality.ResultsA total of 13 studies covering 228 cases of EBV infection among 1157 diseased patients were included. Summary estimates were computed using random-effects model. The pooled prevalence of EBV infection was 20.3% (95% CI: 10.8–34.9, I² ?= ?92.26, p ?< ?0.001). When stratified according to the type of disease, higher estimates were obtained for patients suffering from Kaposi's sarcoma (98.7%, 95% CI: 82.2–99.9) and Nasopharyngeal malignancy (85.7%, 95% CI: 70.0–93.9). A prevalence of 13.4% (95% CI: 6.0–27.4) and 12.2% (95% CI: 4.8–27.8) was derived for the most reported patient populations, lymphoma and HIV, respectively.ConclusionThis first meta-analysis on the prevalence of EBV among Nigerian patients suffering from various diseases reveals a prevalence that emphasises the need to routinely monitor EBV infection in all EBV-associated diseases in Nigeria.     

Cognitive Impairments in Patients with Bipolar Affective Disorder in Remission

Neuroscience and Behavioral Physiology - Objective. To determine the frequency, structure, and severity of cognitive impairments in patients with bipolar affective disorder (BAD) in remission....     

The role of cytokines in determining the Th1/Th2 phenotype of an immune response: Coherence of the T cell response and the Cytokine Implementation Hypothesis

The widely accepted Cytokine Milieu Hypothesis proposes that the cytokine milieu, in which antigen activates CD4 T cells, from a non-T cell source, primarily determines the Th subset to which the ensuing effector Th cells belong. We focus on the generation of Th1 and Th2 cells. We briefly restate the grounds for the Threshold Hypothesis we favour for how the Th1/Th2 phenotype of a response is primarily determined: tentative and robust thresholds of antigen-mediated CD4 T cell interactions lead to the generation of Th1 and Th2 cells. The component antigens of pathogens are present in different amounts. It is expected, within the context of the threshold mechanism that, although there is often an initial predominance of Th1 or Th2 cells, some Th cells of the opposing type are initially generated. An initially somewhat heterogeneous Th response is known to become with time more ‘coherent’ in its Th1/Th2 phenotype. I propose The Cytokine Implementation Hypothesis as a mechanism for how coherence is achieved. Most cytokines made by Th cells of one subset tend to facilitate the further generation of Th cells of this subset and/or inhibit the generation of Th cells of opposing subsets, accounting for how coherence may be achieved. Many observations on which The Cytokine Milieu Hypothesis is based are accounted for by this alternative hypothesis. We outline predictions of the new hypothesis and discuss the importance of coherence of immune responses for their efficacy in protecting against foreign invaders.