Design and development of 6-hydrazinonicotinyl-fatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent

Abstract The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTc-complexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.

Radiofármacos en medicina nuclear del INAMEN en la gestión 2021 / Radiopharmaceuticals in nuclear medicine of INAMEN in 2021

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.

Application of automatic injection device based on automatic hemostasis in injection of radiopharmaceutical bolus injection / 生物医学工程学杂志

In clinical practice, radiopharmaceutical dynamic imaging technology requires the bolus injection method to complete injection. Due to the failure rate and radiation damage of manual injection, even experienced technicians still bear a lot of psychological burden. This study combined the advantages and disadvantages of various manual injection modes to develop the radiopharmaceutical bolus injector, and explored the application of automatic injection in the field of bolus injection from four aspects: radiation protection, occlusion response, sterility of injection process and effect of bolus injection. Compared with the current mainstream manual injection method, the bolus manufactured by the radiopharmaceutical bolus injector based on the automatic hemostasis method had a narrower full width at half maximum and better repeatability. At the same time, radiopharmaceutical bolus injector had reduced the radiation dose of the technician's palm by 98.8%, and ensured more efficient vein occlusion recognition performance and sterility of the entire injection process. The radiopharmaceutical bolus injector based on automatic hemostasis has application potential in improving the effect and repeatability of bolus injection.

Global progress in peptide radiopharmaceutical research and China's opportunities / 药学学报

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.

Application of Radiopharmaceuticals in Targeted Tumor Therapies / 中国生物化学与分子生物学报

Radiopharmaceuticals are radionuclide preparations or radiolabelled compounds used for clinical diagnosis or treatment. The targeted radionuclide therapy uses molecular carriers with high affinity for tumor cells to target radionuclides into specific tumor tissues to treat tumors. Compared with traditional radiotherapy and chemotherapy, it is more selective. With the development of nuclear medicine, the popularization of SPECT/CT, PET/CT, the discovery of new targets and the development of new radiopharmaceuticals, the targeted therapy with radiopharmaceuticals is playing an increasingly important role in the clinical treatment of tumors. This review briefly describes the classification, composition and characteristics of radiopharmaceuticals; the application of radioimmunodrugs targeting tumor-associated antigen in non-Hodgkin's lymphoma, colorectal cancer and prostate cancer; the clinical application of receptor-mediated radionuclide drugs in the treatment of neuroendocrine tumors, prostate cancer and breast cancer, and the research progress of radiopharmaceuticals based on gene modification in targeted tumor therapies. Finally, the application prospects and challenges of radiopharmaceuticals in cancer treatment are summarized in order to provide some references for the development and clinical application of radiopharmaceuticals for targeted tumor therapy.

Preliminary study on assessment of internal dose to workers exposed to 131I radionuclide / 中华放射医学与防护杂志

Objective:To explore the assessment methodology for internal dose to workers exposed to 131I radionuclide. Methods:Workers were chosen in a 131I radiopharmaceutial manufacturer and a nuclear medicine department in a hospital using 131I to treat hyperthyroidism and thyroid cancer. A portable high purity germanium (HPGe) gamma spectrometer was used to measure the content of 131I in the thyroid for 4 consecutive times in a period of 7 d. The internal dose was estimated combining with the work rotation mode for workers dealing with 131I. Results:When the monitoring month was used as a typical month to estimate the internal dose, the annual committed effective dose was 0.09-1.93 mSv for the production staff engaged in the repackaging of 131I radiopharmaceuticals in the surveyed enterprise, and 0.06-0.58 mSv for the nuclear medicine staff in the surveyed hospital. After adjusting the monitoring result of the current monitoring period based on the rotation mode, the annual committed effective dose was estimated to be 0.06-1.22 mSv for radiopharmaceutical production workers and 0.03-0.15 mSv for nuclear medicine workers, respectively. Conclusions:In the assessment of internal dose to radiation workers exposed to 131I, using a single time measurement result to estimate the annual dose would lead to a larger error. In the case of continuous monitoring, the result of subsequent monitoring periods should be corrected according to the result of previous monitoring periods. In order to accurately estimate the internal dose of workers exposed to 131I, it is necessary to take full account of the 131I exposure pattern, time and frequency and the internal contamination route. For workers who may be exposed to 131I with potential internal dose greater than 1 mSv/year, a 14 day-routine monitoring period was appropriate.

Synthesis method optimization and biodistribution study of 18F-T807 on TRACERlab FXFN synthesizer / 药学实践杂志

Objective To optimize the synthesis method of 18F-T807 and study preliminary biodistribution. Methods 18F-T807 was synthesized using an optimized method in TRACERlab FXFN synthesizer with a t-BOC（t-Butyloxy carbonyl）-protected 18F-T807 precursor NPPI-9 as starting material, improving experimental conditions for synthesis, then QC and biodistribution study in Wistar rats conducted. Results The improved synthesis conditions increased the synthesis yield from 20.5%±6.1% to 25.7%±5.8%. QC met the standard. Wistar rats had higher intake in kidney, liver, blood and lowest intake in brain, heart, lung. Conclusion The optimized synthesis method to synthesize 18F-T807 is simple and easy, and high yield, which can meet the needs of scientific research and clinical practice.

Design and Test of Automatic Dispensing and Injecting System for Positron Radiopharmaceuticals / 中国医学科学院学报

Objective To design a novel automatic dispensing and injecting system of positron radiopharmaceuticals,for precise dose dispensing,simplified operation,and reduction of occupational radiation exposure. Methods The automatic dispensing and injecting system was fabricated with tungsten alloy as the shielding material.The performance and radiation protection of the device were assessed. Results The total time of injection using the automatic dispensing and injecting system was about 60 s.The ratio of successful injection in stability test was 100%.The deviation of the dispensing dose with the system was ≤3%.With the tungsten alloy shield(40 mmPb of the cabinet,60 mmPb of the countertop,15 mmPb of the protective shield,and 50 mmPb of the inbuilt jar for radiopharmaceuticals),the average dose rate at 30 cm from the device was 1.44 μSv/h,and the radiation dose at the operator's extremity was reduced by 99%. Conclusions This automatic dispensing and injecting system of positron radiopharmaceuticals is easy to operate with precise dispensing dose.It is safe and meets the requirements of radiation protection.

Preliminary study of fogging process for fixing high-concentration radioactive aerosol 131I contamination in a radiopharmaceutica production unit / 中国辐射卫生

Objective To prove the feasibility of a Fogging Process in fixing high-concentration radioactive aerosol 131I contamination. Methods High-concentration radioactive aerosol 131I contamination in an 131I-operating glovebox for radiopharmaceutical production was disposed by using fogging and fixing process. The aerosol 131I concentrations were detected and the results were analyzed. Results After a 120 minutes fixing, the 131I contamination in this glovebox reduced from(289 ± 9) DAC and (304 ± 6) DAC to (21.7 ± 2.0) DAC and (26.2 ± 1.8) DAC. After a 180 minutes fixing, the 131I contamination in this glovebox reduced from (259 ± 10) DAC to (1.80 ± 0.18) DAC. These results showed that no aerosol 131I contamination was raised again after 24-hours finishing this task. Conclusion Aerosol 131I concentration in a limited space could be controlled by using a fogging and fixing process, which could reduce the risk of internal exposure of staff. This process could be used by radiopharmaceutical production as an emergency management for dispose high-concentration radioactive aerosol 131I contamination.

Diagnostic Reference Levels for Adult Nuclear Medicine Imaging Established from the National Survey in Korea / 대한핵의학회잡지

PURPOSE: There is substantial need for optimizing radiation protection in nuclear medicine imaging studies. However, the diagnostic reference levels (DRLs) have not yet been established for nuclear medicine imaging studies in Korea.MATERIALS AND METHODS: The data of administered activity in 32 nuclear medicine imaging studies were collected from the Korean Society of Nuclear Medicine (KSNM) dose survey database from 2013 and 2014. Through the expert discussions and statistical analyses, the 75th quartile value (Q3) was suggested as the preliminary DRL values. Preliminary DRLs were subjected to approval process by the KSNM Board of Directors and KSNM Council, followed by clinical applications and performance rating by domestic institutes.RESULTS: DRLs were determined through 32 nuclear medicine imaging studies. The Q3 value was considered as appropriate selection as it was generally consistent with the most commonly administered activity. In the present study, the final version of initial DRL values for nuclear medicine imaging in Korean adults is described including various protocols of the brain and myocardial perfusion imaging.CONCLUSION: The first DRLs for nuclear medicine imaging in Korean adults were confirmed. The DRLs will enable optimized radiation protection in the field of nuclear medicine imaging in Korea.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

Treatment of Bone Metastasis with Bone-Targeting Radiopharmaceuticals / 대한핵의학회잡지

Bone is a common metastatic site of cancer. Bone metastasis reduces life expectancy and results in serious symptoms and complications such as bone pain, pathological fractures, and spinal cord compression, decreasing quality of life by restricting sleep and mobility. Treatment for bone metastasis includes drugs (pure analgesics, hormones, cytotoxic chemotherapy, and bisphosphonates, among others), external radiation therapy, surgery, and radionuclide therapy using bone-targeting radiopharmaceuticals. Particulate radiation with α- or β-rays is used as a bone-targeting radiopharmaceutical in radionuclide therapy. β-Emitters have lower energy and a longer range than α-emitters and have less tumoricidal activity and deliver more radiation to adjacent normal tissue. Therefore, the main therapeutic effect of bone-targeting β-emitters such as ⁸⁹Sr-dichloride is bone pain palliation rather than enhanced survival. In contrast, α-emitters such as ²²³Ra-dichloride have high energy and a short range, resulting in greater tumoricidal activity and less radiation damage to adjacent normal tissue. Treatment with bone-targeting α-emitters can improve survival and decrease bone pain. This review focuses on the principles and clinical utility of several clinically available bone-targeting radiopharmaceuticals in metastatic bone disease.

Development of tau PET Imaging Ligands and their Utility in Preclinical and Clinical Studies / 대한핵의학회잡지

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

Radiation protection and safety in nuclear medicine / 中国医学影像技术

The clinical nuclear medicine can be used for disease diagnosis and treatment,however,in the diagnosis and treatment process,the patient becomes a source of radiation not only to him/herself,but also to the general public and medical staff,which has been a topical subject with the public awareness of radiation protection gradually.How we scientifically regard the radiation will help promote the development of nuclear medicine,and eliminate the fear of the public.The radiation protection and safety is an important part of clinical nuclear medicine and the development of fine disciplines.The new ideas and knowledge about radiation protection and safety of patients,public and nuclear medical staff in recent years were reviewed in this article.

Laser stimulation of the acupoint ‘Zusanli’ (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the ‘Zusanli’ acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na99mTcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm2) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na99mTcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

Introduction to the national drug standards of radiopharmaceutical preparations and the main revision in the Chinese Pharmacopoeia 2015 edition / 中国药学杂志

The author summarized the national drug standards of radiopharmaceutical preparations and analyzed the existing problems, and gave a brief introduction about the revision in the Chinese Pharmacopoeia 2015 edition.

Diagnostic use of neuro-spect quantified with 99m Tc-ECD a model based on normal data / Uso de neuro-spect quantificado com 99m Tc-ECD: um modelo baseado em dados normais

OBJECTIVE: The purpose of the present study was to prospectively quantify the normal limits of brain perfusion using specific software in a group of asymptomatic young volunteers submitted to single-photon emission tomography (SPECT) with 99m Tc-ethyl cysteinate dimer (99m Tc-ECD). METHODS: We used 15 MBq/kg of intravenous 99m Tc-ECD in 30 healthy volunteers submitted to brief neuropsychological tests and a clinical questionnaire. These data were normalized relative to the cerebellum (Group 1) and to the brain cortex (Group 2). Statistical analysis was performed with Student's t-test. The average radioactivity was 6.5 million counts/study. RESULTS: The normalized (Group I) revealed an average value of 78.03%, with standard deviation (SD) of 4.07. Two volunteers in this group had slightly greater than two standard deviations from the mean. When we used (Group II), the average value was 71.01%, with a SD of 4.66. We observed a difference between groups of 9% (P<0.001). CONCLUSION: The present study suggests normal cortical perfusional values for a group of young asymptomatic volunteers, utilizing 99m Tc-ECD. This allows further quantification of neuro-SPECT data, specifically comparisons across patient populations. Furthermore, this method represents a new tool that can be used to further explore the of neuroimaging, particularly neuropsychiatry.

OBJETIVO: O objetivo do presente estudo foi quantificar prospectivamente os limites normais de perfusão cerebral utilizando software específico em um grupo de jovens voluntários assintomáticos submetidos a tomografia por emissão de fóton Único (SPECT) com 99m Tc-etil cisteinato dímero (99m Tc-ECD). MÉTODOS: Foram utilizados 15 MBq/kg intravenoso de 99m Tc-ECD em 30 voluntários sadios submetidos a uma bateria breve de testes neuropsicológicos e questionário clínico. Estes dados foram normalizados para o cerebelo (Grupo 1) e no córtex cerebral (Grupo 2). A análise estatística foi obtida através do teste T de Student. A atividade média foi de 6,5 milhões de contagens/estudo. RESULTADOS: A normalização (Grupo I) revelou um valor médio de 78,03%, com um desvio-padrão (DP) de 4,07. Dois voluntários neste grupo tiveram valores ligeiramente maiores do que dois desvios padrões da média. Quando utilizado (Grupo II), o valor médio foi de 71,01%, com um desvio padrão de 4,66. Observou-se uma diferença entre grupos de 9% (P<0,001).CONCLUSÃO: O presente estudo sugere valores corticais perfusionais normais para um grupo de jovens voluntários assintomáticos, utilizando 99m Tc-ECD. Isto permite ainda a quantificação dos dados de neuro-SPECT, especificamente a comparação entre populações de pacientes. Além disso, este método apresenta uma nova ferramenta que pode ser usada para explorar ainda mais o campo da neuroimagem, particularmente em neuropsiquiatria.

Suggestion of a national diagnostic reference level for 18F-FDG/PET scans in adult cancer patients in Brazil / Sugestão de nível de referência em diagnóstico nacional para 18F-FDG/PET em procedimentos oncológicos adultos no Brasil

Objective To suggest a national value for the diagnostic reference level (DRL) in terms of activity in MBq.kg–1, for nuclear medicine procedures with fluorodeoxyglucose (18F-FDG) in whole body positron emission tomography (PET) scans of adult patients. Materials and Methods A survey on values of 18F-FDG activity administered in Brazilian clinics was undertaken by means of a questionnaire including questions about number and manufacturer of the installed equipment, model and detector type. The suggested DRL value was based on the calculation of the third quartile of the activity values distribution reported by the clinics. Results Among the surveyed Brazilian clinics, 58% responded completely or partially the questionnaire; and the results demonstrated variation of up to 100% in the reported radiopharmaceutical activity. The suggested DRL for 18F-FDG/PET activity was 5.54 MBq.kg–1 (0.149 mCi.kg–1). Conclusion The present study has demonstrated the lack of standardization in administered radiopharmaceutical activities for PET procedures in Brazil, corroborating the necessity of an official DRL value to be adopted in the country. The suggested DLR value demonstrates that there is room for optimization of the procedures and 18F-FDG/PET activities administered in Brazilian clinics to reduce the doses delivered to patients. It is important to highlight that this value should be continually revised and optimized at least every five years. .

Marcado con 99m de liposomas convencionales y su evaluación biológica / 99mTc-labeling and biological evaluation of conventional liposomes

Introducción. Los liposomas son sistemas supramoleculares autoensamblables preparados ad hoc, compuestos de fosfolípidos y colesterol, diseñados para transporte de fármacos o radionucleidos. El 99mTc es el radionucleido más empleado por sus propiedades físicas apropiadas para la adquisición de imágenes y estudios en pacientes en el área de medicina nuclear (emisor gamma puro con E = 140 KeV , t1/2 = 6 horas). Objetivo. Evaluar la potencialidad de liposomas convencionales marcados con 99mTc como agente de diagnóstico de procesos tumorales. Método. La composición estudiada es: fosfatidilcolina, dioleilfosfatidiletanolamina y colesterol (1.1:0.4:1 relación molar). Se utilizó como agente reductor SnF2, en diferentes cantidades para optimizar el marcado. La pureza radioquímica y eficiencia de marcado se evaluaron con sistemas cromatográficos ITLC-SG FM NaCl 0,9 por ciento, ITLC-SG FM Piridina:ácido acético:agua (3:5:1.5 v/v). Se adquirieron imágenes a 1 h post inyección de los liposomas en ratones sanos y portadores de tumor mamario espontáneo. Resultados. El liposoma marcado mostró estabilidad durante 24 h, siendo la cantidad óptima de reductor 138 ug. La mejor captación en tumor fue a 1 h post administración del radiofármaco en los estudios centellográficos. Conclusiones. El método optimizado permite obtener liposomas marcados con 99mTc en forma sencilla, eficiente y estable. Estos radiofármacos mostraron un comportamiento fiscoquímico y biológico adecuado como agentes de diagnóstico tumoral requiriéndose estudios posteriores para su confirmación.

Background. Liposomes are self-assembled supramolecular systems, composed by phospholipids and cholesterol, designed for the transportation of drugs or radionuclides. Physical properties of 99mTc (pure gamma emitter with E = 140 KeV, t1/2= 6 hours) makes it useful for scintigraphic imaging. Purpose. The goal of this study was to evaluate 99mTc labeled conventional liposomes as potential diagnostic agents for malignant lesions. Methods. The studied liposome composition was hosphatidylcholine: dioleilphosphatidylcholine: cholesterol (1.1:0.4:1molar rate). In order to optimize the labeling, SnF2 was used as reducing agent. Radiochemical purity and labeling efficiency were evaluated using ascending thin layer chromatography. Scintigraphy images were obtained at 1 hour post-injection of labeled liposomes to healthy mice and with spontaneous breast tumors. Results. Labeled liposomes showed stability during 24 hours, being 138 ug the optimal amount of reducing agent for the technique used. Conclusions. The described method allows the production of 99mTc labeled liposomes in a simple, efficient and stable way. The radiopharmaceutical showed a physicochemical and biological behavior that allows its potential use as a tumor imaging agent, although further studies are required to confirm this issue.