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This study investigated how a standard could become reality-based in a workplace where certain types of deviations are not permitted, such as a radiopharmaceutical production unit. Compliance with standards is necessary to ensure the safety of individuals who manufacture such substances as well as the security of patients receiving treatment. In this qualitative case study, an ergonomic analysis of work (also known as activity analysis) was performed, with noncompliance recorded in internal audits as a starting point: the lack of double-checking in radiopharmaceutical synthesis cassette assembly. Field observations and self-confrontation interviews with workers from a production unit were conducted to analyze the activities. Although a double-check did not occur, the radiopharmaceutical synthesis operator apparently developed another risk control strategy, focusing his attention to the equipment assembly details, which necessitated continuous control and verification actions to ensure that there were no problems at this stage of production. A multilevel approach was used to demonstrate how the safety and quality of production processes based on standard compliance only become effective and adherent to the activity after resolving various conflicts at work, including control systems (external and internal audits), work collectives, the contradiction of the activity itself, and the discussion of singular situations arising daily. This study contributes to the discussion on workplace safety considering standardization and advances the discussion on changing perspectives regarding rule compliance.

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ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians' preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

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Introducción : Una de las áreas de la farmacia vinculadas a la radiación ionizante es la Radiofarmacia que se refiere al estudio, preparación, control y dispensación de los radiofármacos a nivel industrial y hospitalaria. Se entiende como radiofármaco a cualquier producto que esté preparado para su uso con la finalidad diagnóstica y terapéutica que contenga uno o más radionucleidos (isótopos radioactivos) que son utilizados en combinación con moléculas o solos para ser administrados por vía oral o parenteral. El Instituto Nacional de Medicina Nuclear (INAMEN) a nivel nacional lidera ese campo desde 1962 al servicio de la población boliviana. Objetivo : Determinar el uso y diagnóstico de los radiofármacos que son utilizados con mayor frecuencia en medicina nuclear en el INAMEN en la gestión 2021. Metodología : Estudio descriptivo y retrospectivo donde se analizaron los reportes de solicitud de preparación y dispensación de radiofármacos en el laboratorio de Radiofarmacia del INAMEN. Estos datos fueron procesados para determinar que radiofármacos son los más demandados para el diagnóstico y terapia medica nuclear en nuestro departamento. Resultados . Se determinó que de las 2100 solicitudes presentadas al laboratorio de Radiofarmacia, el 42% corresponde al metilen difosfonato-99mTc, el 21% corresponde a los isotopos de 99mTc y el 11% corresponde al isotopo 131I. Conclusión . El análisis de los datos concluye que la principal demanda de radiofármacos es para radiotrazadores de tumores y para la yodoterapia.

Introduction : One of the areas of pharmacy linked to ionizing radiation is Radiopharmacy, which refers to the study, preparation, control and dispensing of radiopharmaceuticals at an industrial and hospital level. A radiopharmaceutical is understood as any product that is prepared for use for diagnostic and therapeutic purposes that contains one or more radionuclides (radioactive isotopes) that are used in combination with molecules or alone to be administered orally or parenterally. The National Institute of Nuclear Medicine (INAMEN) at the national level has led this field since 1962 at the service of the Bolivian population. Objective : Determine the use and diagnosis of the radiopharmaceuticals that are most frequently used in nuclear medicine in the INAMEN in the 2021 administration. Methodology : Descriptive and retrospective study where the reports requesting the preparation and dispensing of radiopharmaceuticals in the INAMEN Radiopharmacy laboratory were analyzed. These data were processed to determine which radiopharmaceuticals are the most in demand for nuclear medical diagnosis and therapy in our department. Results : It was determined that of the 2100 applications submitted to the Radiopharmacy laboratory, 42% correspond to methylene diphosphonate-99mTc, 21% correspond to 99mTc isotopes and 11% correspond to 131I isotopes. Conclution : The analysis of the data concludes that the main demand for radiopharmaceuticals is for tumor radiotracers and iodotherapy.

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The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be -2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

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Relative biological effectiveness is a radiobiological parameter relevant in radiotherapy planning and useful in evaluating the physiological impact of radiation in different tissues. Targeted radionuclide therapy allows the selective and specific deposition of higher radiation doses in a noninvasive way and without collateral effects through the administration of radiopharmaceuticals. Lu-DOTA-177(hydrazinylnicotinoyl-Lys-(Nal)-NH-CO-NH-Glu) also called Lu-iPSMA177 is a third generation radiopharmaceutical composed by a peptide that recognizes the prostate-specific membrane antigen (PSMA), a membrane protein overexpressed in several types of cancer and that mediates the radiopharmaceutical's recognition of cancer cells. The present study reports radiobiological parameters of Lu-iPSMA177 and demonstrates the superiority of targeted radiopharmaceuticals over external radiotherapy treatment options in terms of their relative biological effectiveness. The relative biological effectiveness value of 1.020±0.003 for the LINAC, estimated by fitting the linear-quadratic model equation to the resulting survival curves, was like those of 1.25±0.04,1.060±0.005and1.00±0.04 obtained by an alternative method in relation to the mean lethal doses at 90, 80 or 60 survival percent respectively. While the relative biological effectiveness values of 5.65±0.13,4.72±0.27and2.87±0.19 estimated for Lu-iPSMA177 were significantly higher than those for the LINAC. The results confirm that the biological effect produced by the deposition of a radiation absorbed dose delivered by the LINAC can be induced with a quarter of that dose using Lu-iPSMA177 due to the energy distribution, dose-rate and energy fluence.

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Metalloproteinase-9 (MMP-9) is a key protein in cancer advancement and metastasis owing to its ability to degrade some extracellular matrix components. Mangiferin, a natural polyphenolic compound, has demonstrated through experimental and theoretical studies to be a great anticancer agent for the selective inhibition of MMP-9. This work aimed to evaluate the utility of several fluorinated compounds obtained from MF as possible Positron Emission Tomography (PET) radiopharmaceuticals oriented to MMP-9. Density Functional Theory calculations of MF were made to obtain the most active sites toward electrophilic and nucleophilic reactions and propose a synthetic route to produce its fluorinated derivatives. The reactivity study allowed us to propose a late-stage synthetic route based on click chemistry to obtain three fluorinated MF-based derivatives. Molecular docking calculations suggested that the derivative F-propyl-MF could be suitable as PET radiopharmaceutical owing to the establishment of a five-coordinated complex with the catalytic Zn atom belonging to the active site of MMP-9, crucial factor in the inhibition of MMP-9.

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Nanotechnology has changed the world, with a great impact on industry and medicine. In this commentary, we discuss the importance of radiolabeled nanomaterials for the construction of theranostic, imaging and therapeutic agents in order to pave the future of medicine.

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Ionizing radiation has been used for decades and expanded to several applications in multivariate sectors, becoming an important tool to promote controlled chemical reactions in polymeric structures, according to their chemical properties for developing new materials. In addition, the use of radiation can also be applied in order to reduce or eliminate compounds from solutions that may be harmful or of low interest. In this review, we overviewed the chemistry behind material irradiation and the attractive use of ionizing radiation in scientific and industrial development. In this regard, the review was divided into three main sections titled (1) chemical kinetics intermediated by radiation, (2) chemical bonds intermediated by radiation, and (3) radiation chemistry on polymers. We concluded that graft polymerization, crosslinking and chain scission reactions induced by ionizing radiation are very efficient and green strategies for developing new materials with improved properties. Furthermore, water radiolysis plays a key role in the degradation of several contaminants, including pharmaceuticals and microplastics, in aqueous solutions. However, more studies must be conducted to complement the existing theory about the proposed mechanisms responsible for modifying the chemical, mechanical, thermal, optical, and so forth properties of irradiated materials.

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ABSTRACT Molecular imaging markers can be used to differentiate between infection and aseptic inflammation, determine the severity of infection, and monitor treatment responses. One of these markers is ubiquicidin(29-41) (UBI), a cationic peptide fragment that binds to the bacterial membrane wall and is labeled with gallium-68 (68Ga), a positron emitter radioisotope. The use of UBI in positron emission tomography (PET)/computed tomography (CT) for improved detection of lesions has been receiving considerable attention recently. Herein, we report the first case of 68Ga-UBI PET/CT performed in Brazil. The patient was a 39-year-old woman referred for a scan to confirm a clinical suspicion of chronic osteomyelitis of her fractured left tibia. PET images revealed radiotracer uptake near the posterior contour of the tibial fracture focus and the fixation plate, in the soft tissue around the distal half of the tibia, and in the non-consolidated fracture of the left distal fibula. Surgery for local cleaning was performed, and culture of a specimen collected from the surgical site confirmed the presence of Staphylococcus aureus. In the present case, 68Ga-UBI PET/CT, a non-invasive imaging modality, identified the infection foci in vivo, indicating its potential for clinical use.

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In the last years, new insights into the molecular basis of rheumatic conditions have been described, which have generated particular interest in understanding the pathophysiology of these diseases, in which lies the explanation of the diversity of clinical presentation and the difficulty in diagnostic and therapeutic approaches. In this review, we focus on the new pathophysiological findings for Sjögren syndrome and on the derived new SPECT and PET radiopharmaceuticals to detect inflammation of immunological origin, focusing on their role in diagnosis, prognosis, and the evaluation of therapeutic efficacy.

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The study identified occupational exposure in the work of radiology technologists with 68Ga radiopharmaceuticals, in a Nuclear Medicine service in southern Brazil, by means of observation and document analysis. The occupational exposure related the factors, distance, time and shielding. Thus, it was observed high times during handling of the material, small distances between sources and radiosensitive structures, such as the eye lens and the thyroid gland. It is recommended to reassess and standardize the work, once that critical moments should not be restricted only to dosimetric reading.

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Rapamycin (or sirolimus) is a macrolide that has shown to be useful as an immunosuppressant and that was studied in metabolic, neurological, or genetic disorders. Rapamycin is a specific natural inhibitor of the mechanistic target of rapamycin (mTOR) that is a kinase protein playing a pivotal role in cell growth and proliferation by activation of several metabolic processes. This work aimed to evaluate the utility of several compounds obtained from rapamycin and its semi-synthetic analogs everolimus and temsirolimus as possible radiopharmaceuticals oriented to this protein. Density Functional Theory calculations of these molecules were made and further analysis of the dual descriptor, charges populations, and of the electrostatic potential surfaces were performed. Molecular docking simulations were used to evaluate the interactions of the rapamycin with the studied candidates. They allowed us to propose two strategies for the synthesis of novel compounds based on electrophilic reactions. Molecular docking results also helped us to eliminate molecules that did not interact correctly with the target. Finally, we found for the first time, that the novel compounds synthesized through the electrophilic addition reaction that employed 18F-selectfluor, should maintain the biological activity of original compounds and could be suitable as Positron Emission Tomography radiopharmaceuticals targeting mTOR Complex1 system.

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The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.

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This study sought to evaluate the types and frequencies of nuclear medicine studies that were carried out at a privately-run nuclear medicine facility in Kingston, Jamaica. Previous studies of this nature have not been done among this population, therefore the researchers sought to gather data which may prove to be useful for the growth of nuclear medicine practice in Jamaica. The study was a nonexperimental, retrospective study which involved an assessment of the records of all nuclear medicine patients who received a radiopharmaceutical during January 01, 2017, to December 31, 2018. The data extracted included age, gender, radiopharmaceutical administered, indication for study, and impression from scan. The total number of nuclear medicine scans that were carried out at the facility for the 2-year period was 3756. Of this number, 1889 (50.3%) were male and 1866 (49.7%) were female, with the age ranging from 3 months to 100 years. The types and frequencies of the most frequently occurring studies conducted were bone (2116, 56.3%), renal (867, 23.1%), thyroid (307, 8.2%), and lung (254, 6.8%). Patients aged 60 years and over accounted for the majority of the bone scans (1353/2116). The age group 26-59 years accounted for most of the scans of the lung (123/254), thyroid (209/307), parathyroid (34/65), and whole body (26/34). Patients under 12 years of age accounted for the majority of the renal (596/867), gastrointestinal (22/26), and hepatobiliary (16/28) scans. The audit of this private facility reflects the documented demand on the International Atomic Energy Agency database for Latin America and the Caribbean, and demonstrates the need for continuity of this specialized service in our population.

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The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient's quality of life.

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Resumen Introducción: En 2009, el Instituto Nacional de Cancerología (INC) elaboró el 177Lu-DOTATATE/TOC. El propósito del estudio fue demostrar la eficacia de estos radiopéptidos en el tratamiento paliativo de pacientes con tumores neuroendocrinos (TNE) avanzados inoperables (metastásicos o localmente avanzados) y en progresión. Métodos: Ensayo clínico abierto fase II de un solo brazo en 13 pacientes adultos con TNE grado 1 o 2, con expresión de receptores de somatostatina en lesiones blanco demostrada por captación Krenning 3 o 4 en 99mTc-HYNIC TOC. Los pacientes fueron tratados con 177Lu-DOTATATE o 177Lu-DOTATOC (según disponibilidad) a una actividad acumulativa proyectada de 600-800 mCi dividida en 3-4 dosis cada 6-9 semanas comenzando siempre con una actividad fija de 200 mCi y dosimetría con la primera dosis. El desenlace primario fue la respuesta objetiva calculada 6 y 12 meses después de la última dosis del tratamiento. Resultados: Se incluyeron 13 pacientes (7 mujeres) de 63 ± 11,6 años con TNE avanzado inoperable y en progresión. La actividad final administrada fue de 800 mCi, 600 mCi, 400 mCi y 200 mCi en 4, 7, 1 y 1 pacientes, respectivamente. La tasa de control de enfermedad a 6 y 12 meses fue de 69,2% y 45,5%, respectivamente, logrando únicamente enfermedad estable. Fallecieron 7 pacientes, 2 de ellos en los primeros 6 meses. La mediana de supervivencia global a partir de la última dosis del radiopéptido fue de 15,7 meses. Conclusiones: Se corroboró la eficacia y la seguridad del tratamiento con los radiopéptidos en NETs avanzados.

Abstract Objectives: The National Cancer Institute first elaborated 177Lu-DOTATATE/TOC in 2009. The purpose of this study was to prove the efficacy of these radiopeptides in the palliative treatment of patients with progressive advanced inoperable neuroendocrine tumors (NETs). Methods: A single-phase phase II open clinical trial was conducted in 13 adult patients with grade 1 y 2 NETs, with expression of somatostatin receptors in target lesions proven by Krenning Score 3 or 4 uptake in 99mTc-HYNIC TOC. Patients were treated with 177Lu-DOTATATE or 177Lu-DOTATOC (depending upon availability) at a projected acumulative activitiy of 600-800 mCi divided into 3-4 doses every 6-9 weeks always beginning with a fixed activity of 200 mCi and dosimetry during the first dose. The primary outcome was objective response to therapy. Results: 13 patients (7 women) aged 63 ± 11.6 years with inoperable advanced NETs were included. The final therapeutic administered activity was 800 mCi, 600 mCi, 400 mCi and 200 mCi in 4, 7, 1 and 1 patients, respectively. The disease control rate at 6 and 12 months was 69.2% and 45.5%, respectively, only obtaining stable disease. Six patients died, 2 of them in the first 6 months. Median overall survival was 15.7 months from the last treatment dose. Conclusions: The efficacy of the treatment with 177Lu-DOTATATE or 177Lu-DOTATOC radiopeptides elaborated in-house was confirmed, becoming a management alternative for patients with advanced NETs.

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Resumen Próximo a su 25 aniversario CENTIS reflexiona sobre su quehacer en el contexto de los trastornos que causa la COVID-19. Con ese propósito se examinan el estado de la medicina nuclear y la radiofarmacia antes y durante la epidemia y sus perspectivas de desarrollo. La producción global de radiofármacos continúa siendo una industria consolidada y aunque la pandemia afecta a esta esfera, la presencia de otras enfermedades no cesa, por lo que los servicios de medicina nuclear esenciales y críticos siguen siendo necesarios. Se espera su paulatina reapertura y que se retome con más fuerza la investigación, dado que la COVID-19 es tan compleja y se asocia a tantos factores que constituye, en perspectiva, terreno virgen para las técnicas diagnósticas en medicina nuclear. Ha de permanecer asimismo el papel de los radiofármacos terapéuticos en un grupo importante de enfermedades, en cáncer sobre todo. El Centro de Isótopos pone por ello énfasis tanto en la consolidación, bajo buenas prácticas, de la producción y el suministro de radiofármacos, como en el desarrollo de nuevos productos. Ambos aspectos se basan principalmente en dos radionúclidos: Tc-99m e Y-90.

Abstract Close to its 25th anniversary, CENTIS evaluates its work in the context of the disorders triggered by COVID-19. For this purpose, the situation of nuclear medicine and radiopharmacy, before and during the epidemic and their current development prospects is examined. The production of radiopharmaceuticals continues to be a consolidated global industry and although the pandemic affects this area, the presence of other diseases does not cease, so essential and critical nuclear medicine services are still needed, therefore its gradual reopening is expected. In addition, research will be taken with more strength, given that COVID-19 is so complex and associated with so many factors that it constitutes virgin terrain in perspective for diagnostic techniques in nuclear medicine. The role of therapeutic radiopharmaceuticals in an important set of diseases, especially cancer, will also remain. As a result, the Isotope Center focus its attention under good management practices, on the consolidation of the production and distribution of radiopharmaceuticals and in the development of new products. Both aspects are mainly based on two radionuclides: Tc-99m and Y-90.

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Assays that rely on the assessment of frequency of micronuclei are important standard techniques currently used to quantify potential genotoxic damage after exposure to chemical or physical agents, such as ionizing radiation, or in pre-clinical studies, to assessment of the genotoxic potential of drugs or its components. The experiments are usually performed using conventional microscopy, but currently the protocols are being upgraded to automated approaches based on flow cytometry protocols based on the elimination of the plasma membrane by chemical agents, allowing quantification by flow cytometry. In this work, the genotoxic potential of peptides used as components of radiopharmaceuticals (PSMA-617 and 11 and Ubiquicidine) was evaluated exposing CHO-KI cells to a wide range of concentration (0.1X and 100X the maximum allowed concentration to human adults). Incubation with PSMA-11 or UBI29-41 did not induce genotoxicity. After 24 h of incubation, PSMA-617 induced genotoxicity only in non-practical concentration (100-fold). Results corroborate the safety of the pre-drugs and the wide detection range of technique.

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ABSTRACT Objective To expose the current situation of the Brazilian Nuclear Medicine in relation to innovation, taking into account the Intellectual Property protection and the particularities of this field. Methods The number and the origin of patents filings from Brazil, United States and European Patent Convention countries were retrospectively compared in a 20-year period. Results The number of accumulated patents filings of conventional pharmaceuticals was ten times higher compared to the radiopharmaceuticals in the three regions studied. Conclusion The largest number of Brazilian patents filings corresponded to the international patent applications, which is related to the country development conditions, as well as to the difficulties in the process of patent filing.

RESUMO Objetivo Evidenciar a situação atual da Medicina Nuclear brasileira em relação à inovação, considerando a proteção à Propriedade Intelectual e suas particularidades na área. Métodos Foi realizado um levantamento comparativo do número e da origem de depósitos de patentes relacionadas a essa área no Brasil, nos Estados Unidos e em países participantes da European Patent Convention , em um período de 20 anos retroativos. Resultados O número de depósitos acumulados de patentes de medicamentos convencionais foi dez vezes maior quando comparado às famílias relacionadas aos processos que envolvem radiofármacos, nas três regiões estudadas. Conclusão O maior número de depósitos de patentes brasileiras correspondeu aos pedidos de patentes internacionais, refletindo as condições de desenvolvimento do país, bem como as dificuldades encontradas no processo de depósito de uma patente.

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El presente trabajo es una revisión bibliográfica y actualización de los diferentes esquemas terapéuticos aprobados y en estudio, de la enfermedad con metástasis en hueso producto del cáncer de próstata avanzado con la condición de resistente a la castración. Aborda generalidades del cáncer de próstata, los mecanismos por los cuales se vuelve resistente a la castración, la aparición de metástasis óseas, la terapéutica enfocada en terapia antiresortiva, (bifosfonatos e inhibidor del Ligando RANK), radiofármacos, radioterapia y nuevas drogas (Cabozantinib)(au)

This is a literature review and update of the different therapeutic options approved and under study, of bone metastases due to castration resistant prostate cancer. It addresses general information of prostate cancer, the mechanisms by which it becomes resistant to castration, the appearance of bone metastases, treatment focused on antiresorptive therapy (bisphosphonates and RANK Ligand inhibitor), radiopharmaceuticals, radiotherapy and new drugs (Cabozantinib).(au)

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