The Radiopharmaceutical Chemistry of Fluorine-18: Nucleophilic Fluorinations

The positron-emitting radionuclide fluorine-18 plays a prominent role in radiopharmaceuticals for positron emission tomography (PET) due to its favourable nuclear decay properties. Depending on the production method, 18F can be obtained in two different chemical forms: electrophilic [18F]fluorine gas and nucleophilic [18F]fluoride. Nucleophilic [18F]fluoride exhibits several advantages with respect to accessibility and chemical handling. Therefore, nucleophilic 18F-substitution reactions are of pivotal importance for the production of PET radiotracers. This chapter is devoted to this class of reactions, and in the following pages, we seek to provide a general overview of 18F itself as well as insights into nucleophilic 18F-substitution reactions. More specifically, the prerequisites for this reaction with regard to solvent, leaving groups, reactants, etc. are examined. Furthermore, several examples are discussed which demonstrate the potential of this reaction to create highly clinical relevant PET tracers. Finally, this chapter also provides practical tips and tricks for those performing this reaction in the laboratory

Treatment consideration and manifest complexity in comorbid neuropsychiatric disorders

Psychiatric disorders may co-occur in the same individual. These include, for example, substance abuse or obsessive-compulsive disorder with schizophrenia, and movement disorders or epilepsy with affective dysfunctional states. Medications may produce iatrogenic effects, for example cognitive impairments that co-occur with the residual symptoms of the primary disorder being treated. The observation of comorbid disorders in some cases may reflect diagnostic overlap. Impulsivity, impulsiveness or impulsive behaviour is implicated in a range of diagnostic conditions including substance abuse, affective disorder and obsessive-compulsive disorder. These observations suggest a need to re-evaluate established diagnostic criteria and disorder definitions, focusing instead on symptoms and symptom-profiles

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

Objective. Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease. Methods. Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment. Results. This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1-2, and DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28\%, 42\%, and 48\%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35\%, 54\%, and 63\%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs. Conclusion. With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others