Recently, promising results of the antitumor effects were observed in patients with metastatic castration-resistant prostate cancer treated with 177Lu-labeled PSMA-ligands. Radionuclide therapy efficacy may even be improved by using the alpha emitter Ac-225. Higher efficacy is claimed due to high linear energy transfer specifically towards PSMA positive cells, causing more double-strand breaks. This study aims to manufacture [225Ac]Ac-PSMA-I&T according to good manufacturing practice guidelines for the translation of [225Ac]Ac-PSMA-I&T into a clinical phase 1 dose escalation study. Quencher addition during labeling was investigated. Quality control of [225Ac]Ac-PSMA-I&T was based on measurement of Fr-221 (218 keV), in equilibrium with Ac-225 in approximately six half-lives of Fr-221 (T½ = 4.8 min). Radio-(i)TLC methods were utilized for identification of the different radiochemical forms, gamma counter for concentration determination, and HPGe-detector for the detection of the radiochemical yield. Radiochemical purity was determined by HPLC. The final patient dose was prepared and diluted with an optimized concentration of quenchers as during labeling, with an activity of 8–12 MBq (±5%), pH > 5.5, 100 ± 20 μg/dose, PSMA-I&T, radiochemical yield >95%, radiochemical purity >90% (up to 3 h), endotoxin levels of <5 EU/mL, osmolarity of 2100 mOsmol, and is produced according to current guidelines. The start of the phase I dose escalation study is planned in the near future.

For patients with metastatic castration-resistant prostate cancer (mCRPC), the survival benefit of classic treatment options with chemotherapy and drugs targeting androgen signaling is limited. Therefore, beta and alpha radionuclide therapy (RNT) have emerged as novel treatment options for patients with mCRPC. Radioligands target the prostate-specific membrane antigen (PSMA) epitopes, which are upregulated up to a thousand times more in prostate cancer cells compared to the cells in normal tissues. For this reason, PSMA is an excellent target for both imaging and therapy. Over the past years, many studies have investigated the treatment effects of lutetium-177 labeled PSMA (177Lu-PSMA) and actinium-225 labeled PSMA (225Ac-PSMA) RNT in patients with mCRPC. While promising results have been achieved, this field is still in development. In this review, we have summarized and discussed the clinical data of 177Lu-PSMA and 225Ac-PSMA RNT in patients with mCRPC.

BackgroundAddressing the obesity epidemic requires the development of effective interventions aimed at increasing physical activity (PA). eHealth interventions with the use of accelerometers and gaming elements, such as rewarding or social bonding, seem promising. These eHealth elements, blended with face-to-face contacts, have the potential to help people adopt and maintain a physically active lifestyle.ObjectiveThe aim of this study was to assess the influence and usage of a blended Web-based gaming intervention on PA, body mass index (BMI), and waist circumference among overweight and obese employees.MethodsIn an uncontrolled before-after study, we observed 52 health care employees with BMI more than 25 kg/m2, who were recruited via the company’s intranet and who voluntarily participated in a 23-week Web-based gaming intervention, supplemented (blended) with non-eHealth components. These non-eHealth components were an individual session with an occupational health physician involving motivational interviewing and 5 multidisciplinary group sessions. The game was played by teams in 5 time periods, aiming to gain points by being physically active, as measured by an accelerometer. Data were collected in 2014 and 2015. Primary outcome was PA, defined as length of time at MET (metabolic equivalent task) ≥3, as measured by the accelerometer during the game. Secondary outcomes were reductions in BMI and waist circumference, measured at baseline and 10 and 23 weeks after the start of the program. Gaming elements such as “compliance” with the game (ie, days of accelerometer wear), “engagement” with the game (ie, frequency of reaching a personal monthly target), and “eHealth teams” (ie, social influence of eHealth teams) were measured as potential determinants of the outcomes. Linear mixed models were used to evaluate the effects on all outcome measures.ResultsThe mean age of participants was 48.1 years; most participants were female (42/51, 82%). The mean PA was 86 minutes per day, ranging from 6.5 to 223 minutes, which was on average 26.2 minutes per day more than self-reported PA at baseline and remained fairly constant during the game. Mean BMI was reduced by 1.87 kg/m2 (5.6%) and waist circumference by 5.6 cm (4.8%). The univariable model showed that compliance, engagement, and eHealth team were significantly associated with more PA, which remained significant for eHealth team in the multivariable model.ConclusionsThis blended Web-based gaming intervention was beneficial for overweight workers in becoming physically active above the recommended activity levels during the entire intervention period, and a favorable influence on BMI and waist circumference was observed. Promising components in the intervention, and thus targets for upscaling, are eHealth teams and engagement with the game. Broader implementation and long-term follow-up can provide insights into the sustainable effects on PA and weight loss and into who benefits the most from this approach.

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