BACKGROUND:Latin America faces a high dementia burden, with increased prevalence of factors associated with cognitive decline. Multidomain lifestyle interventions might delay cognitive decline, but populations from Latin America remain under-represented in dementia prevention trials. We aimed to investigate the feasibility of a culturally adapted, multidomain, systematic lifestyle intervention and investigate its effects on global cognitive function in at-risk older adults (aged 60-77 years). METHODS:The LatAm-FINGERS Initiative for Cognitive Change (hereafter referred to as LatAm-FINGERS) was a single-blind, multicentre, randomised clinical trial conducted in 11 Latin American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Peru, and Uruguay). Individuals aged 60-77 years with high risk of dementia (cardiovascular risk factors, ageing, and dementia risk score ≥6), and suboptimal cognitive performance were randomly assigned (1:1) to receive either a 2-year systematic lifestyle intervention (SLI group) or a flexible lifestyle intervention (FLI group). Randomisation was stratified by the study centre to ensure balance and implemented using permuted blocks of eight. Participants and intervention staff were not masked to group assignment, but individuals who assessed outcomes were masked throughout the trial. The SLI provided structured multidomain lifestyle interventions with supervised support and monitoring; FLI offered health advice. Primary outcomes were trial feasibility (evaluated using selected RE-AIM measures: Reach, Implementation, and Maintenance) and the intervention's effects on global cognitive composite trajectories over 2 years (change in the global cognitive composite score over 2 years). This trial is registered at ClinicalTrials.gov (NCT06492967) and has been completed. FINDINGS:Participants were enrolled between Oct 27, 2021, and July 7, 2023; the last participant completed follow-up on Nov 7, 2025. Among 1719 assessed, 1065 participants included in the analytic sample were randomly assigned to the SLI group (n=539) or the FLI group (n=526). Mean age was 67·5 years (SD 4·7), 795 (75%) of 1065 participants were women, and 270 (25%) were men. Self-reported race and ethnicity were: 624 (59%) Mestizo, 288 (27%) White, 72 (7%) Mulatto, 25 (2%) Mixed or other, 18 (2%) Black, 14 (1%) Indigenous, and 24 (2%) did not report race or ethnicity. 877 (82·3%) of 1065 completed the 2-year follow-up. Recruitment effectiveness (Reach) was 62·0%; mean adherence to the SLI group (Implementation) was 71·6% over the entire trial; and frequencies of complete cognitive outcomes data (Maintenance) were 87·9% at 6 months, 85·3% at 12 months, 81·4% at 18 months, and 84·8% at 24 months in the SLI group compared with 86·3% at 6 months, 78·9% at 12 months, 73·4% at 18 months, and 79·8% at 24 months in the FLI group. Dropouts were higher in the FLI group than in the SLI group (20·2% vs 15·2%; p=0·042). Global cognitive composite scores increased over time in both groups, with a mean annual change of 0·31 SD (95% CI 0·28-0·34) per year in the SLI group and 0·20 SD (0·17-0·23) per year in the FLI group (mean between-group difference of 0·11 SD per year [0·06-0·15; p<0·0001]). Overall, 478 adverse events were reported (412 in the SLI group and 66 in the FLI group). The most common adverse events were musculoskeletal symptoms (113 [21%] in the SLI group, 13 [2%] in the FLI group), upper respiratory infections (50 [9%] in the SLI group, one [<1%] in the FLI group), and COVID-19 infection (31 [6%] events in the SLI group). Serious adverse events occurred in 50 (9%) participants in the SLI group and 24 (5%) participants in the FLI group; none were related to the intervention. There were eight deaths (three in the SLI group and five in the FLI group), and none were related to the intervention. INTERPRETATION:A culturally adapted multidomain lifestyle intervention was feasible across Latin America and resulted in greater cognitive improvements than a flexible health-advice intervention in older adults at risk of cognitive decline. These findings extend the evidence base for multidomain lifestyle interventions to populations historically under-represented in dementia research, supporting their feasibility and scalability as strategies to reduce cognitive decline risk amid the rapidly growing burden of dementia in low-income and middle-income countries. FUNDING:Alzheimer's Association. TRANSLATIONS:For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Introduction The increasing demand for radiopharmaceuticals at the Centro Uruguayo de Imagenología Molecular (CUDIM), for both diagnostic and therapeutic purposes, has created significant challenges in the safe and efficient handling of incoming and outgoing products. Traditional workflows were not designed to cope with the growing complexity of production, distribution, traceability, safety and health requirements from different customers. To address these issues, a dedicated radiopharmaceutical logistics unit within the Radiopharmacy Department was created on January 2024. Objectives The main objective was to ensure a robust and safe supply chain of 177Luthetium radiopharmaceuticals and 223RaCl2, in agreement with national and international regulations. Materials and Methods The radiopharmaceutical logistics unit was designed to integrate key processes including: (1) standardized reception of radiopharmaceuticals and radionuclides, (2) internal distribution protocols aligned with clinical schedules, (3) external dispatch to pre-registered customers, and (4) a digital tracking system to ensure batch traceability and compliance with Good Manufacturing Practice (GMP). Results Following the incorporation of the logistics unit, the management of scheduled treatments was optimized for all radiopharmaceuticals, considering the entire process starting from the radionuclide/radiopharmaceutical request, customs clearance, reception, preparation, quality control, batch release, and coordination and delivery to the clinical area when applicable. This improvement in processes occurred alongside a 224% increase in the reception of Lu-177 between 2023 and 2024, and a further 322% increase vs ten months of 2025. Coordination with clinical services improved markedly since dedicated staff in the unit and in the clinical sector were assigned. Training of specialized staff and the development of standard operating procedures (SOPs) were central in the implementation phase. Furthermore, the new system enabled CUDIM to expand its radiopharmaceutical supply to external institutions. Additionally with the creation of the unit 15 new documents were developed, including 5 Standard Operating Procedures (SOPs) and 10 record forms, reinforcing process standardization and operational traceability in the framework of CUDIM’s QMS. Conclusion The establishment of a dedicated logistics unit in radiopharmacy proved to be a critical innovation to meet the increasing demands of nuclear medicine services related to theranosis. This experience highlights that logistics integration is essential to ensure safety, efficiency, and sustainability in the management of radiopharmaceuticals Funding Acknowledgements Centro Uruguayo de Imagenología Molecular - CUDIM
Introduction Theranostics, the integrated use of molecular imaging and targeted radionuclide therapy, is transforming precision oncology worldwide. In Uruguay, the Uruguayan Center for Molecular Imaging (CUDIM) has created a dedicated multidisciplinary Theranostics Unit to optimize delivery, follow-up, evaluation, and clinical interaction with prescriptors, as well as expanding access to advanced radionuclide therapies. Although national integration across other national institutions and key stakeholders is still in progress, it is advisable to develop a strong international collaborations with such as ARCAL programs of the International Atomic Energy Agency, the International Centers for Precision Oncology (ICPO) and the Oncidium Foundation to support have accelerated implementation, capacities training, and research innitiatives with a suitable and well trained workforce in this emerging field. Objectives To consolidate a robust and sustainable multidisciplinary theranostics structure at the national level, supported by international partnerships that ensure quality, safety, training, and continuous innovation in targeted molecular therapies. Materials and Methods The Unit integrates nuclear medicine, oncology, radiopharmacy, physics, radioprotection, and information systems within CUDIM’s GMP-certified environment. Operational protocols were standardized for ¹77Lu-PSMA, ¹77Lu-DOTATATE, and ²²³RaCl2 therapies, having ²²5Ac, 161Tb radiopharmaceuticals and ¹77Lu-FAPI in the pipeline. A centralized patient follow-up system was developed to ensure traceability and safety. Collaboration with IAEA, ICPO and Oncidium enables participation in educational programs, protocol harmonization, and cooperative research aimed at generating regional evidence and training future professionals. Results The Unit successfully implemented a unified clinical and radiopharmaceutical workflow, reducing treatment delays and ensuring adherence, in agreement with international quality standards. Over 100 therapeutic procedures have been performed with ¹77Lu and ²²³Ra, achieving high response rates and excellent safety profiles (<5% adverse events ≥G3). Continuous internal audits confirmed full compliance with GMP/GDP standards in the radiopharmacy deparment.Educational activities and workshops have initiated the training of multidisciplinary teams, while international partnerships expanded visibility and access to cutting-edge knowledge. Two-market authorization were achieved by the Drug Department of the Ministry of Health. The first national registry of theranostic patients was created enabling the basis for clinical research and longitudinal follow-up. Conclusion The CUDIM Theranostics Unit demonstrates that sustained progress in molecular therapy can be achieved through a multidisciplinary approach enriched by international collaboration. This initiative positions the Uruguayan Center for Molecular Imaging as an emerging regional reference in theranostics and highlights the importance of cooperative frameworks to integrate innovation, education, and translational research into routine clinical practice. Funding Acknowledgements Supported by Uruguayan Center for Molecular Imaging (CUDIM)
Introduction During the COVID-19 pandemic, Uruguayan patients receiving ²²³RaCl (Xofigo®) abroad faced barriers to continuing treatment. In response, the Uruguayan Center for Molecular Imaging (CUDIM) initiated the national implementation of ²²³RaCl, an alpha-emitting radiopharmaceutical for patients with metastatic castration-resistant prostate cancer (mCRPC). Treatments began under a compassionate-use framework, with individual approval from the National Drug Regulatory Authority (Ministry of Health).The implementation process started in 2021, achieving all operational, clinical, radioprotection, and quality-assurance requirements. Following formal market authorization, since August 2025 CUDIM has become the sole center in Uruguay authorized to administer ²²³RaCl in partnership with the manufacturing laboratory, ensuring national access to targeted alpha therapy (TAT) within the public healthcare network under a private-law framework. Objectives To describe the implementation process and early clinical outcomes of ²²³RaCl therapy in Uruguay, within a multidisciplinary theranostics program operating under a quality-assurance system. Materials and Methods Based on a five-year institutional experience with therapeutic radiopharmaceuticals, CUDIM formally established its Theranostics Unit in June 2025. The unit was structured as an integrated workflow encompassing nuclear medicine, clinical oncology, radiopharmacy, and radiation safety. All procedures adhered to GMP/GDP standards, including individualized dosimetry, radiopharmaceutical traceability, and systematic clinical follow-up.Patients with symptomatic bone-dominant mCRPC and no visceral metastases were treated in accordance with international guidelines (55 kBq/kg IV every 4 weeks, up to six cycles). Baseline and per-cycle clinical and biochemical assessments were performed. Results From August to October 2025, five patients completed a total of 20 ²²³RaCl administrations without logistical or procedural complications. Pain relief occurred in 80% of patients, with improved quality of life and reduced opioid requirements in 60%. No grade ≥3 hematologic toxicity was observed; mild anemia and leukopenia resolved spontaneously.The implementation strategy enabled the development of national standard operating procedures, safety checklists, and a digital registry for treatment and outcomes. Supply-chain reliability was secured through coordination with the pharmaceutical provider and national regulatory bodies. Conclusion CUDIM successfully established ²²³RaCl therapy in Uruguay through institutional commitment, interdisciplinary collaboration, and strict regulatory compliance. By 2025, Uruguay achieved national autonomy in delivering targeted alpha therapy for mCRPC. This experience represents a scalable model for integrating advanced radionuclide therapies into public healthcare systems while ensuring safety, quality and equitable access. Funding Acknowledgements Supported by the Uruguayan Center for Molecular Imaging (CUDIM), Montevideo, Uruguay.
Introduction Novel therapeutic radionuclides are advancing targeted radiotherapy towards more precise and effective approaches. ¹⁶¹Tb (terbium-161) stands out for its unique physical and radiobiological properties, combining β⁻ emission advantages of isotopes like ¹⁷⁷Lu with internal conversion and Auger electron emission. These low-energy electrons deposit energy over extremely short distances, enabling highly localized destruction of tumor cells, particularly in micrometastases and single cancer cells. ¹⁶¹Tb also shares chemical characteristics with ¹⁷⁷Lu, allowing the use of existing targeting molecules and radiolabeling methods.Targeted alpha therapy (TAT) with ²²⁵Ac (actinium-225) provides potent cytotoxicity for advanced tumors and resistant micrometastases via α-particle emission. Combined or sequential application of ¹⁶¹Tb, ¹⁷⁷Lu, and ²²⁵Ac represents a multimodal, personalized approach aiming to maximize efficacy while minimizing adverse effects. Objectives To evaluate the efficacy of radioligand therapies based on ¹⁶¹Tb, ¹⁷⁷Lu, and ²²⁵Ac, individually or combined, in a preclinical prostate cancer model, exploring strategies that maximize antitumor effect while minimizing toxicity. Materials and Methods In vitro properties of [²²⁵Ac]Ac-PSMA-617 and [¹⁶¹Tb]Tb-PSMA-617 were assessed in LNCaP (PSMA+) and PC3 (PSMA-) cells via antiproliferative, binding, cytotoxicity, and clonogenic assays.In vivo, de-escalated actinium-225/lutetium-177-PSMA-617 “cocktail” regimens were tested to improve tolerability. A five-branch study comparing control group with: [¹⁷⁷Lu]Lu-PSMA-617, [²²⁵Ac]Ac-PSMA-617, their combination, [¹⁶¹Tb]Tb-PSMA-617 and control were performed in a xenograft nude mouse model. Tumor growth was monitored by caliper measurements and PET-CT with [¹⁸F]F-AlF-PSMA-11 over two months. Results [²²⁵Ac]Ac-PSMA-617 and [¹⁶¹Tb]Tb-PSMA-617 showed specific, dose-dependent inhibition of LNCaP proliferation; effects in PC3 cells required higher activity. Autoradiography confirmed higher affinity for LNCaP cells. Cytotoxicity and colony formation assays showed greater LNCaP sensitivity, consistent with PSMA expression. In vivo, beta and alpha radiopharmaceuticals improved survival and tumor growth rates versus controls, with tumor absence in some cases. The [¹⁶¹Tb]Tb-PSMA-617 group is ongoing, therefore comparative efficacy in tumor size and survival will be presented. Conclusion PSMA-targeted radioisotope therapy and combined TAT could improve disease management by delaying progression, emphasizing the need for further studies to optimize administration schemes according to patient status and lesion type. Funding Acknowledgements Centro Uruguayo de Imagenología Molecular
