Purpose Pridopidine is an investigational drug for Huntington disease (HD). Pridopidine was originally thought to act as a dopamine stabilizer. However, pridopidine shows highest affinity to the sigma-1 receptor (S1R) and enhances neuroprotection via the S1R in preclinical studies. Using [18F] fluspidine and [18F] fallypride PET, the purpose of this study was to assess in vivo target engagement/receptor occupancy of pridopidine to the S1R and dopamine D2/D3 receptor (D2/D3R) at clinical relevant doses in healthy volunteers (HVs) and as proof-of-concept in a small number of patients with HD. Methods Using [18F] fluspidine PET (300 MBq, 0–90 min), 11 male HVs (pridopidine 0.5 to 90 mg; six dose groups) and three male patients with HD (pridopidine 90 mg) were investigated twice, without and 2 h after single dose of pridopidine. Using [18F] fallypride PET (200 MBq, 0–210 min), four male HVs were studied without and 2 h following pridopidine administration (90 mg). Receptor occupancy was analyzed by the Lassen plot. Results S1R occupancy as function of pridopidine dose (or plasma concentration) in HVs could be described by a three-parameter Hill equation with a Hill coefficient larger than one. A high degree of S1R occupancy (87% to 91%) was found throughout the brain at pridopidine doses ranging from 22.5 to 90 mg. S1R occupancy was 43% at 1 mg pridopidine. In contrast, at 90 mg pridopidine, the D2/D3R occupancy was only minimal (~ 3%). Conclusions Our PET findings indicate that at clinically relevant single dose of 90 mg, pridopidine acts as a selective S1R ligand showing near to complete S1R occupancy with negligible occupancy of the D2/D3R. The dose S1R occupancy relationship suggests cooperative binding of pridopidine to the S1R. Our findings provide significant clarification about pridopidine’s mechanism of action and support further use of the 45-mg twice-daily dose to achieve full and selective targeting of the S1R in future clinical trials of neurodegenerative disorders. Clinical Trials.gov Identifier: NCT03019289 January 12, 2017; EUDRA-CT-Nr. 2016-001757-41.

Purpose Cardio-pulmonary damage due to embolism is a feared complication of cemented hip arthroplasty and can be fatal. Embolic events result from an increased intramedullary pressure during cement and stem insertion and can lead to extrusion of bone-marrow elements into the circulation. To reduce embolism and at the same time achieve an ideal cement mantle, the cement injection stem has been designed. In contrast to conventional stems where cement applied before stem insertion (primary cementing technique), the cement injection stem is positioned first and only then is the cement injected via the stem in a volume-and pressure-controlled fashion (secondary cementing technique). Methods A randomised trial with 30 patients was performed to evaluate whether this technique is able to reduce embolic events. Patients either received a conventional cemented stem (primary cementing technique) or a cement injection stem (secondary cementing technique). Embolic events were recorded by transesophageal echocardiography at six specific points during the operation and classified from grade 0 to grade 3.Results Significantly fewer grade 2 and 3 embolic events were observed in patients receiving the cement injection stem using the secondary cementing technique. Moreover, in the conventional group all patients (100 %) had at least one grade 3 embolus whereas only 20 % with the secondary cementing technique had an embolic event of grade 3. Conclusion Secondary cement insertion via the cement injection stem is able to reduce severe embolic events significantly. The technique offers a more gentle cementing technique and therefore appears especially beneficial for patients of advanced age and/or with pre-existing cardiopulmonary comorbidities.

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