In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric ß-D-Glucopyranosyltriazole.

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.

Cisplatin-Loaded Thermosensitive Liposomes Functionalized with Hyaluronic Acid: Cytotoxicity and In Vivo Acute Toxicity Evaluation.

Cisplatin (CDDP) is a potent antitumor drug used in first-line chemotherapy against several solid tumors, including breast cancer. However, toxicities and drug resistance limit its clinical application. Thermosensitive liposome (TSL) functionalized with hyaluronic acid (HA) containing cisplatin (TSL-CDDP-HA) was developed by our research group aiming to promote the release of CDDP in the tumor region under hyperthermia conditions, as well as to decrease toxicity. Thus, this study aimed to evaluate this new formulation (HA-coated TSL-CDDP) concerning in vitro behavior and in vivo toxicity compared to non-coated TSL-CDDP and free CDDP. Cytotoxicity assays and nuclear morphology were carried out against triple-negative breast cancer cells (MDA-MB-231), while an in vivo toxicity study was performed using healthy Swiss mice. The results showed an increase (around 3-fold) in cytotoxicity of the cationic formulation (non-coated TSL-CDDP) compared to free CDDP. On the other hand, TSL-CDDP treatment induced the appearance of 2.5-fold more senescent cells with alteration of nuclear morphology than the free drug after hyperthermia condition. Furthermore, the association of liposomal formulations treatment with hyperthermia increased the percentage of apoptotic cells compared to those without heating. The percentage of apoptotic cells was 1.7-fold higher for TSL-CDDP-HA than for TSL-CDDP. For the in vivo toxicity data, the TSL-CDDP treatment was also toxic to healthy cells, inducing nephrotoxicity with a significant increase in urea levels compared to the saline control group (73.1 ± 2.4 vs. 49.2 ± 2.8 mg/mL). On the other hand, the HA-coated TSL-CDDP eliminated the damages related to the use of CDDP since the animals did not show changes in hematological and biochemical examinations and histological analyses. Thus, data suggest that this new formulation is a potential candidate for the intravenous therapy of solid tumors.

Enhanced antitumor efficacy of lapachol-loaded nanoemulsion in breast cancer tumor model.

Lapachol (LAP) is a natural compound with various biological properties, including anticancer activity. However, its clinical application is limited due to the low aqueous solubility and potential adverse side effects. Nanoemulsions are drug delivery systems that can assist in the administration of hydrophobic drugs, increasing their bioavailability and protecting from degradation. Thus, this study aimed to prepare a LAP-loaded nanoemulsion (NE-LAP), and evaluate its antitumor activity. For this purpose, the nanoemulsion was prepared using a hot homogenization method and characterized morphologically by cryogenic transmission electron microscopy (cryo-TEM). Mean diameter, polydispersity index, and zeta potential was evaluated by DLS, encapsulation efficiency was measured by HPLC. Moreover, the short-term storage stability, the drug release and hemolysis in vitro was determined. Additionally, pharmacokinetic, toxicology and toxicity properties of99mTc-NE-LAP were evaluated in a breast cancer (4T1) tumor model. The cryo-TEM showed spherical globules, and the physicochemical characterization of NE-LAP showed a homogeneous stable nanoemulsion with a mean diameter of ∼170 nm, zeta potential of around -20 mV, and encapsulation greater than 85 %. In vitro studies validated that encapsulation did not impair the cytotoxicity activity of LAP. The nanoemulsion was successfully radiolabeled and 99mTc-NE-LAP showed prolonged blood circulation and tumor affinity was confirmed by tumor-to-muscle ratio. Moreover, NE-LAP showed higher antitumor activity than the free drug and the treatment did not result in any signs of toxicity. Therefore, these findings suggest that NE-LAP can be considered an effective strategy for cancer treatment.

Planejamento e implementação do curso Sexual Assault Nurse Examiner para o atendimento às vítimas de violência sexual: relato de experiência / Planificación e implementación del curso Sexual Assault Nurse Examiner para asistir a víctimas de violencia sexual: un informe de experiencia / Planning and implementation of the Sexual Assault Nurse Examiner course to assist victims of sexual violence: an experience report

RESUMO Objetivo Descrever a experiência dos autores enfermeiros no planejamento e implementação de um curso de treinamento baseado no Sexual Assault Nurse Examiner. Método Trata-se de um relato de experiência com características qualitativas de natureza descritiva e recorte transversal. No ano de 2019, foram treinados enfermeiros para o atendimento de vítimas de violência sexual por meio de um curso, nos Estados Unidos, conhecido como Sexual Assault Nurse Examiner. O curso teve carga horária de 40 horas e foi oferecido para enfermeiros. As estratégias didáticas utilizadas foram: exposição dialogada, dinâmicas em grupos e simulação realística para o exame clínico-ginecológico com voluntárias. Resultados Durante cinco dias, 20 enfermeiros foram capacitados. Os conteúdos abordados abrangeram a legislação brasileira, protocolos de atendimentos às vítimas, a anamnese, exame físico, coleta e preservação de vestígios forenses. As aulas práticas aconteceram nos dois últimos dias de treinamento. Ao final do curso, aplicou-se uma avaliação escrita. Conclusão O curso oportunizou a consolidação de conhecimentos importantes para o atendimento pelo enfermeiro às vítimas de violência sexual, coleta e preservação de vestígios e participação na cadeia de custódia.

RESUMEN Objetivo Describir la experiencia de enfermeras autoras en la planificación e implementación de un curso de capacitación basado en el Sexual Assault Nurse Examiner. Método Se trata de un relato de experiencia con características cualitativas de carácter descriptivo y de corte transversal. En 2019, se capacitó a enfermeras para atender a víctimas de violencia sexual a través de un curso en los Estados Unidos, conocido como Sexual Assault Nurse Examiner. El curso tuvo una carga de trabajo de 40 horas y se ofreció a enfermeras. Las estrategias didácticas utilizadas fueron: exposición de diálogo, dinámica de grupo y simulación realista para examen clínico-ginecológico con voluntarios. Resultados Durante cinco días se capacitó a 20 enfermeras. Los contenidos cubrieron la legislación brasileña, protocolos de atención a las víctimas, anamnesis, exploración física, recolección y preservación de restos forenses. Las clases prácticas tuvieron lugar en los dos últimos días de formación. Al finalizar el curso se aplicó una evaluación escrita. Conclusión El curso brindó una oportunidad para la consolidación de conocimientos importantes para los enfermeros en la atención de víctimas de violencia sexual, recolección y preservación de huellas y participación en la cadena de custodia.

ABSTRACT Objective To describe the authors' experiences in planning and implementing a training course based on the Sexual Assault Nurse Examiner. Method This is an experience report with qualitative characteristics of a descriptive nature and cross-sectional cut. In 2019, nurses were trained to care for victims of sexual violence through a course known in the United States as Sexual Assault Nurse Examiner. The course lasted 40 hours and was offered to nurses. The didactic strategies used were dialogued exposure, group dynamics and realistic simulation for clinical-gynecological examination with volunteers. Results For five days, 20 nurses underwent training. The contents covered Brazilian legislation, protocols for assisting victims, anamnesis, physical examination, collection and preservation of forensic remains. The practical classes took place in the last two days of training. At the end of the course, a written assessment was applied. Conclusion The course provided the opportunity for the consolidation of important knowledge for nurses to care for victims of sexual violence, collection and preservation of traces and participation in the chain of custody.

Utilização da prática baseada em evidências pelo enfermeiro no serviço hospitalar / Use of evidence-based practice by nurses in the hospital service

Descrever as práticas, atitudes e conhecimento dos enfermeiros hospitalares sobre a Prática Baseada em Evidências.Método: estudo descritivo, com 124 enfermeiros de um hospital universitário de Sergipe, Brasil. Foi aplicado o questionário Evidence-Based Practice Questionnaire, entre janeiro e fevereiro de 2019, e os dados analisados pelos testes de Shapiro-Wilk, Kruskal-Wallis e Post hoc. Resultados: 86,3% dos participantes são do sexo feminino, média de idade de 34,5 anos e tempo de formação entre cinco e dez anos. A pontuação média final para a escala de Prática Baseada em Evidências e Efetividade foi de 115,9, indicando atitudes positivas dos enfermeiros relacionadas à Prática Baseada em Evidências. Conclusão: as atitudes dos enfermeiros são embasadas em resultados científicos, entretanto, nem sempre as melhores evidências são utilizadas no subsídio das práticas profissionais. Difundir o uso adequado da pesquisa na Enfermagem contribui para a segurança do paciente, educação permanente e qualidade da assistência.

Investigation in forensic nursing: trajectories and possibilities of action / La pericia en la enfermería forense: trayectorias y posibilidades de actuación / A perícia na enfermagem forense: trajetórias e possibilidades de atuação

ABSTRACT To theorize and reflect on the possibilities of the forensic nurse's performance, emphasizing the work as a civil and criminal expert, based on the Brazilian legislation, ethical principles, and comprehensive care for human beings. This is a theoretical study of exploratory nature with reflective and critical characteristics. It was based on the history of the national and international development of the forensic nursing specialty. It is organized into four categories, namely: areas of practice of forensic nurses in North American countries; state-of-the-art North American forensic nursing and the Brazilian reality, and nursing action in the face of violence. This way, international history, national panorama, and in-depth theoretical study were concatenated. Evidence of the contribution of forensic nursing to criminal and civil areas points to the emerging need for implementation and recognition of this practice within the scope of forensic investigation in Brazil with the inclusion of the topic in undergraduate courses.

RESUMEM Teorizar y reflexionar sobre las posibilidades de actuación del enfermero forense, con énfasis en su actuación como perito civil y criminal, pautándose en la legislación brasileña, en los principios éticos y en la integralidad del cuidado al ser humano. Es un estudio teórico con características reflexivas y críticas de carácter exploratorio. Se pautó en la historia del desarrollo de la especialidad enfermería forense en el ámbito internacional y nacional. Está organizado en cuatro clases: Áreas de actuación del enfermero forense en países norteamericanos; estado del arte de la enfermería forense norte americana y la realidad brasileña y la actuación del profesional enfermero frente a la violencia. De esta forma se pudo unir la historia internacional, el panorama nacional y el perfeccionamiento teórico. Las evidencias de la contribución de la enfermería forense en las áreas criminales y civiles destacan la necesidad emergente de implementación y reconocimiento de esta práctica en el ámbito de las pericias forenses en Brasil con la inclusión del tema en los cursos de graduación.

RESUMO Teorizar e refletir sobre as possibilidades de atuação do enfermeiro forense, enfatizando a atuação como perito civil e criminal, pautandose na legislação brasileira, nos princípios éticos e na integralidade do cuidado ao ser humano. É um estudo teórico com características reflexivas e críticas de natureza exploratória. Foi pautado na história do desenvolvimento da especialidade de enfermagem forense no âmbito internacional e nacional. Está organizado em quatro categorias, a saber: áreas de atuação do enfermeiro forense em países norteamericanos; estado da arte da enfermagem forense norte americana e a realidade brasileira e atuação do profissional enfermeiro diante da violência. Dessa forma, concatenaram-se a história internacional, panorama nacional e aprofundamento teórico. As evidências da contribuição da enfermagem forense nas áreas criminais e cíveis apontam a necessidade emergente de implementação e reconhecimento dessa prática no âmbito das perícias forenses no Brasil com a inclusão do tema nos cursos de graduação.

Utilização da prática baseada em evidências por enfermeiros no serviço hospitalar / Utilización de la práctica basada en la evidencia por enfermeros en el servicio hospitalario / Use of evidence-based practice by nurses in the hospital service

RESUMO Objetivo: descrever as oráticas, atitudes e conhecimento dos enfermeiros hospitalares sobre a Prática Baseada em Evidências. Método: estudo descritivo, com 124 enfermeiros de um hospital universitário de Sergipe, Brasil. Foi aplicado o questionário Evidence-Based Practice Questionnaire, entre janeiro e fevereiro de 2019, e os dados analisados pelos testes de Shapiro-Wilk, Kruskal-Wallis e Post hoc. Resultados: 86,3% dos participantes são do sexo feminino, média de idade de 34,5 anos e tempo de formação entre cinco e dez anos. A pontuação média final para a escala de Prática Baseada em Evidências e Efetividade foi de 115,9, indicando atitudes positivas dos enfermeiros relacionadas à Prática Baseada em Evidências. Conclusão: as atitudes dos enfermeiros são embasadas em resultados científicos, entretanto, nem sempre as melhores evidências são utilizadas no subsídio das práticas profissionais. Difundir o uso adequado da pesquisa na Enfermagem contribui para a segurança do paciente, educação permanente e qualidade da assistência.

RESUMEN: Objetivo: Describir las prácticas, actitudes y conocimientos de enfermeros hospitalarios sobre Práctica Basada en la Evidencia. Método: Estudio descriptivo, con 124 enfermeros de hospital universitario de Sergipe, Brasil. Fue aplicado cuestionario Evidence-Based Practice Questionnaire, en enero y febrero de 2019. Datos analizados por tests de Shapiro-Wilk, Kruskal-Wallis y Post hoc. Resultados: 86,3% de participantes era de sexo femenino, media etaria de 34,5 años, tiempo de formación entre cinco y diez años. El puntaje promedio final para la escala de Práctica Basada en la Evidencia y Efectividad fue 115,9, indicando actitudes positivas de los enfermeros respecto de la Práctica Basada en la Evidencia. Conclusión: Las actitudes de los enfermeros se basaron en resultados científicos, aunque no siempre las mejores evidencias son utilizadas como respaldo de las prácticas profesionales. Difundir el adecuado uso de la investigación en Enfermería contribuye a la seguridad del paciente, la educación continua y la calidad de atención.

ABSTRACT Objective: To describe the practices, attitudes and knowledge of hospital nurses about Evidence-Based Practice. Method: Descriptive study with 124 nurses from a university hospital in Sergipe, Brazil. The Evidence-Based Practice Questionnaire was applied between January and February 2019, and data were analyzed using Shapiro-Wilk, Kruskal-Wallis and Post hoc tests. Results: Of the total participants, 86.3% are female; the mean age is 34.5 years and the time since graduation ranged from five to ten years. The final average score for the Evidence-Based Practice Questionnaire was 115.9, indicating positive attitudes of nurses related to Evidence-Based Practice. Conclusion: Nurses' attitudes are based on scientific results. However, the best evidence is not always used to support professional practices. Disseminating the appropriate use of research in Nursing contributes to patient safety, permanent education and quality of care.

Encapsulating paclitaxel in polymeric nanomicelles increases antitumor activity and prevents peripheral neuropathy.

Paclitaxel (PTX) has a great clinical significance as an antitumor drug, although several side effects are strongly dose-limiting. In this way, we prepared a PTX-loaded 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] polymeric micelles (PM/PTX) in an attempt to improve safety and effectiveness of conventional PTX formulation (CrEL/EtOH/PTX). In this study, we evaluated from both formulations: stability after dilution, hemocompatibility, cellular uptake, acute toxicity in healthy mice, antitumor activity, and toxicity after multiple-dose treatment. PM/PTX appeared to be more stable than CrEL/EtOH/PTX after dilution. PM/PTX did not exhibit hemolytic activity (values <1%), even at high concentrations. In vitro cellular uptake study indicated that polymeric micelles were able to deliver more PTX (5.8 %) than CrEL/EtOH (2.7 %) to 4T1 cells. In the acute toxicity evaluation in healthy mice, CrEL/EtOH/PTX (single dose of 20 mg/kg) induced peripheral neuropathy, which was not observed in PM/PTX group. Similar results were observed after tumor-bearing mice received a multiple-dose regimen (seven doses of 10 mg/kg). Worth mentioning, we also evaluated vehicles, and CrEL/EtOH alone was not capable of inducing neuropathic pain. Besides, PM/PTX exhibited a higher antitumor activity with an inhibition ratio approximately 1.5-fold higher than CrEL/EtOH/PTX group. This study suggested that PM/PTX is safer than CrEL/EtOH/PTX, and was able to improve the antitumor effectiveness in a 4T1 breast cancer model.

Co-delivery of doxorubicin, docosahexaenoic acid, and α-tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity.

Doxorubicin (DOX) is widely used in cancer treatment, however, its use is often limited due to its side effects. To avoid these shortcomings, the encapsulation of DOX into nanocarriers has been suggested. Herein, we proposed a novel nanostructured lipid carrier (NLC) formulation loading DOX, docosahexaenoic acid (DHA), and α-tocopherol succinate (TS) for cancer treatment. DHA is an omega-3 fatty acid and TS is a vitamin E derivative. It has been proposed that these compounds can enhance the antitumor activity of chemotherapeutics. Thus, we hypothesized that the combination of DOX, DHA, and TS in NLC (NLC-DHA-DOX-TS) could increase antitumor efficacy and also reduce toxicity. NLC-DHA-DOX-TS was prepared using emulsification-ultrasound. DOX was incorporated after preparing the NLC, which prevented its degradation during manufacture. High DOX encapsulation efficiency was obtained due to the ion-pairing with TS. This ion-pairing increases lipophilicity of DOX and reduces its crystallinity, contributing to its encapsulation in the lipid matrix. Controlled DOX release from the NLC was observed in vitro, with increased drug release at the acidic environment. In vitro cell studies indicated that DOX, DHA, and TS have synergistic effects against 4T1 tumor cells. The in vivo study showed that NLC-DHA-DOX-TS exhibited the greatest antitumor efficacy by reducing tumor growth in 4T1 tumor-bearing mice. In addition, this formulation reduced mice mortality, prevented lung metastasis, and decreased DOX-induced toxicity to the heart and liver, which was demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that NLC-DHA-DOX-TS may be a promising carrier for breast cancer treatment.

Sclareol is a potent enhancer of doxorubicin: Evaluation of the free combination and co-loaded nanostructured lipid carriers against breast cancer.

AIMS: In this work, it was sought to determine if there was synergism between doxorubicin (DOX), a well-known antineoplastic, and sclareol (SC), a diterpene from natural origin, in breast cancer treatment. Moreover, it was investigated if their co-loading in the same nanocarrier would result in a gain of activity and/or a toxicity diminishment. MAIN METHODS: The synergism of the DOX:SC combination was evaluated in MDA-MB-231 and 4T1 cells. A nanostructured lipid carrier (NLC) co-encapsulating DOX and SC in their synergistic molar ratio was prepared and characterised, in terms of mean diameter, zeta potential, DOX encapsulation efficiency, small angle X-ray scattering, differential scanning calorimetry, and polarised light microscopy for further intravenous administration. The anticancer activity of the combination, free and encapsulated, was evaluated in 4T1-tumour bearing mice. KEY FINDINGS: It was determined that DOX:SC combination at the molar ratio 1:1.9 presents better synergistic anticancer activity than the molar ratio 1:7.5 in vitro. DOX:SC-loaded NLC (NLC-DOX-SC) improved in vitro cytotoxic and in vivo antitumour activity compared to free DOX. Although NLC-DOX-SC and free DOX:SC, at the synergistic molar ratio, showed similar activity in the in vivo study, the free combination provoked body weight loss, behaviour alterations and haematological toxicity in the animals, while this was not observed for NLC-DOX-SC. SIGNIFICANCE: This work shows that SC and DOX present synergistic anticancer activity for breast cancer treatment whereas NLC-DOX-SC was a feasible alternative to attain the benefits posed by DOX:SC combination but with none to fewer side effects.

Biocontrol agents in the management of Meloidogyne incognita in tomato / Agentes de biocontrole no manejo de Meloidogyne incognita em tomateiro

ABSTRACT: Recognized as prominent among the principal pests of tomato crop, the root-knot nematode (Meloidogyne incognita) has generated much study with regards to control methods. This study aimed to assess the efficiency of biological products in decreasing the M. incognita population in tomato. Four experiments were conducted under greenhouse conditions. Two of these experiments had the purpose to determine the efficiency of NemOut™ (Bacillus subtilis + B. licheniformis + Trichoderma longibrachiatum), and the other two to assess the efficiency of other different biological products in M. incognita management. Tomato plants of the cultivar Santa Cruz Kada Giant were inoculated using 2000 eggs and J2 of M. incognita. In the first two experiments doses corresponding to 0, 4, 6, 8 and 10kg ha-1 of NemOut™ were applied after inoculation. In the second study, the treatments consisted of the use of biological products containing different other biocontrol agents. Assessments were made at 45 and 65 days after inoculation (DAI) to evaluate plant height, fresh shoot and fresh root weigh, gall index and egg mass index, population density and reproduction factor (RF). The NemOut™ doses reduced the M. incognita population density and RF at 45 DAI. The agent Pochonia chlamydosporia showed greater efficiency in controlling M. incognita on tomato. Biological products and the different doses of NemOut™ had no influence on the tomato plant development.

RESUMO: O nematoide das galhas (Meloidogyne incognita) é relatado como uma das principais pragas da cultura do tomate, sendo importante o estudo de alternativas para o seu manejo. O presente estudo objetivou avaliar a eficiência de produtos biológicos na redução da população de M. incognita em tomate. Foram conduzidos quatro experimentos em casa de vegetação, dois visando avaliar a eficiência de doses de NemOut™ (Bacillus subtilis + B. licheniformis + Trichoderma longibrachiatum), e outros dois para avaliar a eficiência de diferentes produtos biológicos no controle de M. incognita. Plantas de tomate Santa Cruz Kada Gigante foram inoculadas com 2000 ovos e J2 de M. incognita. No primeiro estudo foram utilizadas doses equivalentes a 0, 4, 6, 8 e 10kg ha-1 de NemOut™, aplicadas após a inoculação. No segundo estudo os tratamentos constituíram de produtos biológicos com diferentes agentes de biocontrole. As avaliações foram realizadas 45 e 65 dias após a inoculação (DAI), determinando-se altura de plantas, massa fresca da parte aérea e da raiz, índice de galhas e de massas de ovos, densidade populacional e fator de reprodução (FR). Doses crescentes de NemOut™ reduziram a densidade populacional e o FR de M. incognita, aos 45 DAI. O agente Pochonia chlamydosporia mostrou-se mais eficiente no controle de M. incognita no tomateiro. Os produtos biológicos e as diferentes doses de NemOut™ não afetaram o desenvolvimento das plantas de tomate.

Technetium-99m-labeled doxorubicin as an imaging probe for murine breast tumor (4T1 cell line) identification.

OBJECTIVE: Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice. MATERIALS AND METHODS: Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection. RESULTS: The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a ß half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios. CONCLUSION: DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.