Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects.

Em cumprimento aos requisitos normativos e regulatórios, considerados os padrões nacionais e internacionais de Boas Práticas de Fabricação (BPF) de medicamentos, o ambiente de produção de radiofármacos (célula) é determinante para a qualidade do medicamento, quanto aos limites estabelecidos na legislação vigente para níveis de contaminantes, discriminados como partículas não viáveis (partículas em geral) e microrganismos viáveis, corroborado, ainda, pelo fator de decaimento radioativo, uma vez que os radiofármacos devem ser liberados e administrados aos pacientes pouco tempo após sua produção. Tão importante quanto proteger o produto contra uma possível contaminação do meio ambiente é o operador estar protegido contra a contaminação pelo manuseio do produto. Assim, o estudo, concepção e desenvolvimento de uma célula nacional implicou em análises minuciosas de cada um dos elementos de composição do ambiente de produção e de sua operação, orientado pelo conceito de Quality by Design, metodologia que vem sendo aplicada, recentemente, na indústria farmacêutica. O conhecimento do produto, a configuração do espaço de operação por meio de mockup, a abordagem quanto aos atributos críticos da qualidade, com definições claras quanto aos parâmetros do processo produtivo, validados em experimentos, definiram uma célula multipropósito para produção de radiofármacos em acordo com BPF. / In order to fulfill the normative and regulations requirements under the national and international aspects of Good Manufacturing Practices (GMP), the radiopharmaceutical production environment (called \"hot cell\") is determinant for the quality of the medicinal product, within the limits established by the current legislation for levels of contaminants, split into non-viable particles (airborne general particles) and viable microorganisms; in addition to the radioactive decay (called \"half-life\") results radiopharmaceuticals to be released and administered to patients shortly after their production. It is not sufficient to protect the product against possible contamination from the environment, but the operator must be contamination protected when handling the product. Thus, the study, design and development of a national hot cell resulted in detailed analyzes of each single elements of the production environment and its operation, guided by the concept of Quality by Design, which is the methodology that has been applied recently at the pharmaceutical industry. The features such as the product conceptual knowledge, the configuration of the operating space (by mockups), the approaches regarding the quality critical attributes, the clear definitions regarding the parameters of the productive process, and finally the experimental validation, defined a multipurpose hot cell for the production of radiopharmaceuticals according to GMP requirements.

Em cumprimento aos requisitos normativos e regulatórios, considerados os padrões nacionais e internacionais de Boas Práticas de Fabricação (BPF) de medicamentos, o ambiente de produção de radiofármacos (célula) é determinante para a qualidade do medicamento, quanto aos limites estabelecidos na legislação vigente para níveis de contaminantes, discriminados como partículas não viáveis (partículas em geral) e microrganismos viáveis, corroborado, ainda, pelo fator de decaimento radioativo, uma vez que os radiofármacos devem ser liberados e administrados aos pacientes pouco tempo após sua produção. Tão importante quanto proteger o produto contra uma possível contaminação do meio ambiente é o operador estar protegido contra a contaminação pelo manuseio do produto. Assim, o estudo, concepção e desenvolvimento de uma célula nacional implicou em análises minuciosas de cada um dos elementos de composição do ambiente de produção e de sua operação, orientado pelo conceito de Quality by Design, metodologia que vem sendo aplicada, recentemente, na indústria farmacêutica. O conhecimento do produto, a configuração do espaço de operação por meio de mockup, a abordagem quanto aos atributos críticos da qualidade, com definições claras quanto aos parâmetros do processo produtivo, validados em experimentos, definiram uma célula multipropósito para produção de radiofármacos em acordo com BPF. / In order to fulfill the normative and regulations requirements under the national and international aspects of Good Manufacturing Practices (GMP), the radiopharmaceutical production environment (called \"hot cell\") is determinant for the quality of the medicinal product, within the limits established by the current legislation for levels of contaminants, split into non-viable particles (airborne general particles) and viable microorganisms; in addition to the radioactive decay (called \"half-life\") results radiopharmaceuticals to be released and administered to patients shortly after their production. It is not sufficient to protect the product against possible contamination from the environment, but the operator must be contamination protected when handling the product. Thus, the study, design and development of a national hot cell resulted in detailed analyzes of each single elements of the production environment and its operation, guided by the concept of Quality by Design, which is the methodology that has been applied recently at the pharmaceutical industry. The features such as the product conceptual knowledge, the configuration of the operating space (by mockups), the approaches regarding the quality critical attributes, the clear definitions regarding the parameters of the productive process, and finally the experimental validation, defined a multipurpose hot cell for the production of radiopharmaceuticals according to GMP requirements.