Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

Introduction Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. Materials and Methods Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2–8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. Results Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. Discussions Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.

Purpose: Despite the clinical evidence of actinium-225 ( ²²⁵ Ac)-based targeted alpha therapies (TαT) efficacy, optimized treatment regimens are needed to improve overall clinical response rates and decrease toxicities. The nuclear recoil effect of ²²⁵ Ac and its resulting daughter nuclides have been hypothesized to contribute to non-targeted damage. However, a lack of generator concepts for radionuclidically pure francium-221 ( ²²¹ Fr), involvement of strong acids for elution, and its short half-life (4.8 min), has limited in vivo studies. Here, we report on a successful application of an ²²⁵ Ac/ ²²¹ Fr generator concept and the in vivo distribution of ²²¹ Fr and bismuth-213 ( ²¹³ Bi). Methods: The immobilization of ²²⁵ Ac and elution of ²²¹ Fr was performed on a LN2 resin column. The biodistribution of ²²¹ Fr and ²¹³ Bi was investigated in male SCID mice with LNCaP tumors at 5 and 15 min p.i. Results: Our results indicate that LN2 resin is a highly efficient resin for selective separation of ²²⁵ Ac and ²²¹ Fr. The use of 0.1 M NaOAc enabled continuous elution at a constant pH. The biodistribution study revealed a fast distribution of ²²¹ Fr and ²¹³ Bi already 5 min p.i. We observed a strong accumulation of ²²¹ Fr to the kidneys, salivary glands and small intestine. In ²¹³ Bi-injected mice, the highest accumulation was in kidney and liver. Conclusion: We present an unprecedented concept utilizing LN2 resin in ²²⁵ Ac/ ²²¹ Fr generator applications. Successfully eluted and injected ²²¹ Fr fractions showed strong accumulation of ²²¹ Fr and ²¹³ Bi in key organs. Our data provide preliminary evidence of the potential contribution of recoiled progeny radionuclides to side-effects in non-targeted organs.

Receptor scintigraphy gains more interest for diagnosis and treatment of tumors, in particular for neuroendocrine tumors (NET). We used a pan-Bombesin analog, the peptide DOTA-PEG2-[D-tyr6, β-Ala11, Thi13, Nle14] BN(6-14) amide (BZH3). BZH3 binds to at least three receptor subtypes: the BB1 (Neuromedin B), BB2 (Gastrin-releasing peptide, GRP), and BB3. Imaging of ανβ3 integrin expression playing an important role in angiogenesis and metastasis was accomplished with a 68Ga-RGD tetramer. The purpose of this study was to investigate the kinetics and to compare both tracers in an experimental NET cell line. This study comprised nine nude rats inoculated with the pancreatic tumor cell line AR42J. Dynamic positron emission tomography (PET) scans using 68Ga-BZH3 and 68Ga-RGD tetramer were performed (68Ga-RGD tetramer: n = 4, 68Ga-BZH3: n = 5). Standardized uptake values (SUVs) were calculated, and a two-tissue compartmental learning-machine model (calculation of K1 - k4 vessel density (VB) and receptor binding potential (RBP)) as well as a non-compartmental model based on the fractal dimension was used for quantitative analysis of both tracers. Multivariate analysis was used to evaluate the kinetic data. The PET kinetic parameters showed significant differences when individual parameters were compared between groups. Significant differences were found in FD, VB, K1, and RBP (p = 0.0275, 0.05, 0.05, and 0.0275 respectively). The 56- to 60-min SUV for 68Ga-BZH3, with a range of 0.86 to 1.29 (median, 1.19) was higher than the corresponding value for the 68Ga-RGD tetramer, with a range of 0.78 to 1.31 (median, 0.99). Furthermore, FD, VB, K1, and RBP for 68Ga-BZH3 were generally higher than the corresponding values for the 68Ga-RGD tetramer, whereas k3 was slightly higher for 68Ga-RGD tetramer. As a parameter that reflects receptor binding, the increase of K1 for 68Ga-BZH3 indicated higher expression of bombesin receptors than that of the ανβ3 integrin in neuroendocrine tumors. 68Ga-BZH3 seems better suited for diagnosis of NETs owing to higher global tracer uptake.

The development of PSMA-targeting low-molecular-weight hybrid molecules aims at advancing preoperative imaging and accurate intraoperative fluorescence guidance for improved diagnosis and therapy of prostate cancer. In hybrid probe design, the major challenge is the introduction of a bulky dye to peptidomimetic core structures without affecting tumor-targeting properties and pharmacokinetic profiles. This study developed a novel class of PSMA-targeting hybrid molecules based on the clinically established theranostic agent PSMA-617. The fluorescent dye-bearing candidates of the strategically designed molecule library were evaluated in in vitro assays based on their PSMA-binding affinity and internalization properties to identify the most favorable hybrid molecule composition for the installation of a bulky dye. The library’s best candidate was realized with IRDye800CW providing the lead compound. Glu-urea-Lys-2-Nal-Chx-Lys(IRDye800CW)-DOTA (PSMA-927) was investigated in an in vivo proof-of-concept study, with compelling performance in organ distribution studies, PET/MRI and optical imaging, and with a strong PSMA-specific tumor uptake comparable to that of PSMA-617. This study provides valuable insights about the design of PSMA-targeting low-molecular-weight hybrid molecules, which enable further advances in the field of peptidomimetic hybrid molecule development.

Zusammenfassung. Zielsetzung: Die Datenanalyse beschäftigt sich mit der Entwicklung von Suchtnotfällen im Vergleich zu allgemeinpsychiatrischen Notfällen während der COVID-19 Pandemie. Methodik: Es wurden psychiatrische Notfallkontakte in der interdisziplinären Notfallaufnahme der Evang. Kliniken Essen-Mitte für den Zeitraum des Lockdowns vom 15.03.2020 bis zum 04.05.2020 mit den Notfällen im gleichen Zeitraum 2019 verglichen. Suchtassoziierte Notfallkontakte wurden verglichen mit allgemein-psychiatrischen Notfällen unter Berücksichtigung von Alter und Geschlecht. Ergebnisse: Im Untersuchungszeitraum 2020 gab es 387 psychiatrische Notfälle im Vergleich zu 374 im Jahr 2019 (+3.3 %). Die Zahl der suchtassoziierten Notfälle lag 2020 um 25 % höher als 2019, während die Zahl der allgemeinpsychiatrischen Notfälle 2020 um 8,3 % niedriger war als 2019. Der Anteil der abhängigkeitsassoziierten Notfälle, die stationär aufgenommen werden mussten, war 2020 mit 69 % ähnlich hoch wie 2019 (71 %, n. s.). Im Vergleich dazu mussten Patienten mit anderen psychiatrischen Diagnosen 2020 signifikant häufiger aufgenommen werden (65,4 % vs. 52,1 % 2019; chi² = 7,8, p = 0.005). Schlussfolgerungen: Der Anstieg suchtassoziierter Notfälle und eine erhöhte Aufnahmenotwendigkeit der sonstigen psychiatrischen Notfälle unterstreichen die Notwendigkeit, in Krisenzeiten wie der Corona-Pandemie die psychiatrische Notfallversorgung und insbesondere die Versorgung von Suchtnotfällen aufrecht zu erhalten.