The use of real time PCR for arboviruses diagnostics: integrative review / O uso de PCR em tempo real em diagnósticos de arboviroses: revisão integrativa

RESUMEN Las arbovirosis son enfermedades virales transmitidas por artrópodos (arthropod-borne virus). Dengue, zica y chikungunya se destacan entre los arbovirus emergentes y reemergentes en los últimos años en todo el mundo. La similitud de los síntomas de estas infecciones hace que el diagnóstico clínico sea ineficaz, dificultando las medidas profilácticas y preventivas para nuevos brotes. El diagnóstico molecular mediante la técnica de reacción en cadena de la polimerasa (PCR) en tiempo real es una de las formas de diagnosticar esas enfermedades. En este estudio se recopiló y evaluó la literatura sobre el diagnóstico de arbovirosis. Nuestro objetivo era responder a una pregunta orientadora: ¿la metodología de PCR en tiempo real es eficaz para diagnosticar arbovirosis? Se buscaron artículos científicos de acceso abierto en las bases de datos Pubmed (50 artículos) y Scielo (107 artículos), entre 2014 y 2019. La selección se realizó utilizando los criterios de inclusión y exclusión, quedando solo 20 artículos. Entre estos, el 85% fueron estudios transversales, el 10% fueron revisiones sistemáticas y el 5% fueron estudios de casos. El período de publicaciones fue del 50% en 2017; 35% en 2016; y 5% en 2014, 2015 y 2019, cada. En cuanto a los virus tratados en los artículos, el 25% de los estudios investigaron sobre el dengue; el 25% el chikungunya y el 20% el virus del Zica. La efectividad del diagnóstico molecular se publicó en el 21% de los artículos (sensibilidad y especificidad); el 53% destacó el límite de detección; 70%, ausencia de reacciones cruzadas; y el 80%, la diferenciación entre virus.

Descubrimiento de fármacos basado en imagenología de células vivas / Drug discovery based on live cell imaging

RESUMEN El diseño eficiente de compuestos aprovechando las características estructurales de las moléculas y la búsqueda eficiente de dianas terapéuticas, ha proporcionado herramientas efectivas en la investigación de nuevos tratamientos cuando esta se enfoca en mecanismos celulares de la enfermedad. Los cambios fenotípicos producidos por la interacción in vitro entre molécula-diana, pueden controlarse cuantitativamente mediante imagenología de células vivas. Para garantizar una interacción adecuada, es necesario considerar diferentes elementos cruciales: 1. Las características estructurales y la dinámica molecular del compuesto a evaluar. 2. La relevancia del blanco para la fisiopatología de interés. Sin embargo, el desconocimiento del panorama general en el descubrimiento de fármacos, desde problemáticas estructurales y celulares, ha enlentecido la búsqueda de nuevos tratamientos. Esta revisión descriptiva de tema presenta algunos aspectos estructurales importantes para la caracterización de compuestos como candidatos terapéuticos, y aproximaciones experimentales para desarrollo de sistemas celulares. Los tópicos discutidos se enfocan en la monitorización por imagenología de células vivas y así mismo proporcionamos ejemplos relevantes. La monitorización de efectos fenotípicos producidos por interacciones entre candidato químico y blanco terapéutico en un sistema celular puede favorecer la búsqueda eficiente de moléculas potencialmente terapéuticas.

SUMMARY The efficient compounds' design taking advantage of the molecule's structural characteristics and efficient search for therapeutic targets has provided effective tools for the research of new treatments when this is focused on disease cellular mechanisms. Phenotypic changes produced by in vitro interaction between molecules and targets can be monitored quantitatively by live cell imaging. To guarantee adequate interaction, it is necessary to consider different crucial elements: 1. Structural characteristics and molecular dynamics of the evaluated compound. 2. Target relevance for the concern physiopathology. However, overview's ignorance of the drug discovery, from structural and cellular problems, has slowed the new treatments research. This literature review presents some important structural aspects for compounds' characterization as therapeutic candidates and experimental approaches for cellular systems development. Subjects discussed are focused on live cell imaging and we also provide relevant examples. Phenotypic monitoring of interactions' produced effects between the chemical candidate and therapeutic target in a cellular system can favor the efficient search of potentially therapeutic molecules.

In vitro multi-modal imaging of magnetic targeted nanoparticles and their targeting effect on hepatic stellate cells / 中国组织工程研究

BACKGROUND: In recent years, molecular imaging combined with medical imaging technology and targeted molecular probes have gradually become a research focus. The targeted tissues at the molecular level can be observed using molecular imaging, medical imaging technology, and targeted molecular probes in combination to realize non-invasive imaging of the occurrence and development of the diseases. OBJECTIVE: To develop the magnetic targeted nanoparticle probes, observe the ultrasound/CT/MRI imaging properties in vitro, and investigate their targeting ability to rat hepatic stellate cells in vitro. METHODS: Taking poly(lactic-co-glycolic acid) (PLGA) polymer as the shell, cyclic arginine-glycine-aspartic acid (cRGD) octapeptide as the ligand, targeted magnetic nanoparticles with superparamagnetic Fe3O4 embedded in the shell and perfluorooctyl bromide(PFOB) loaded in the core were prepared by double emulsion evaporation method. The physical and chemical properties of the nanoparticles were detected. The ultrasound/CT/MRI multi-modal imaging properties of the nanoparticles at different concentrations diluted with double-distilled water were tested in vitro. Cyclic RGD peptide immobilization on PLGA-Fe3O4-PFOB NPs was completed through the amide condensation reaction. The conjugation efficiency of the cRGD on PLGA-Fe3O4-PFOB NPs and targeting ability of targeted magnetic nanoparticles in vitro were verified. Cytotoxicity experiments were used to measure the toxic effects of nanoparticles at different concentrations on BRL-3A cells in each group. RESULTS AND CONCLUSION: The targeted magnetic nanoparticles with the average size of (221. 5±60. 3) nm were uniform in dispersion and size. The prepared individual nanoparticle was spherical with the superparamagnetic Fe3O4 scattered on the shell. The encapsulation rate of Fe3O4 was 38%. In vitro ultrasound imaging and CT imaging signal decreased gradually as the concentrations of the nanoparticle suspension decreased. The T2-weighted signal of MRI decreased gradually with the increase of the concentrations of magnetic particle Fe3O4. Flow cytometry results showed that 94. 13% of the cRGD was bound to the nanoparticles. In vitro cell targeting experiments showed that compared to PLGA-Fe3O4-PFOB NPs, cRGD-PLGA-Fe3O4-PFOB NPs exhibited greater cell targeting and affinity efficiency to hepatic stellate cells. Cytotoxicity experiments results showed the nanoparticles had no significant influence on cell viability of the BRL-3A cells. These results suggest that targeted magnetic nanoprobe cannot only be used as a multi-modal imaging contrast agent for ultrasound/CT/MRI, but also exhibits a strong specific affinity to rat hepatic stellate cells in vitro. It has great potential for the early diagnosis of liver fibrosis.

Targeting peptide-mediated 131I-polyamidoamine in medullary thyroid carcinoma bearing mice / 中华核医学与分子影像杂志

Objective@#To construct 131I-the fifth generation polyamidoamine (PAMAM(G5.0)) with targeting peptide Ser-Arg-Glu-Ser-Pro-His-Pro (SRESPHP; SR) or Gly-Pro-Leu-Pro-Leu-Arg (GPLPLR; GP) and double targeting peptide SR/GP, and evaluate the targeting ability in medullary thyroid carcinoma (MTC) model.@*Methods@#PAMAM(G5.0), PAMAM(G5.0)-SR, PAMAM(G5.0)-GP and PAMAM(G5.0)-SR/GP were radiolabeled with 131I by chloramine T method. The radiolabeled yield and radiochemical purity were determined by thin layer chromatography. MTC xenografts were developed and the percentage radio-activity of injection dose per gram of tissue (%ID/g) in tumor and organs was measured at 24 h post-injection. Region of interest (ROI) was drawn and the tumor/non-tumor (T/NT) ratios at 4, 8 and 24 h post-injection were calculated and compared among different groups. One-way analysis of variance, repetitive measurement analysis of variance and Dunnett-t test were used to compare the data of different groups. The relationship between %ID/g and T/NT was analyzed with Pearson correlation.@*Results@#The radiolabeled yield was more than 75% and radiochemistry purity was more than 90%. The difference of %ID/g at 24 h post-injection was significant (F=14.400, P<0.001) in tumors of all groups. The radioactive uptake in tumor of 131I-PAMAM(G5.0)-SR group was the highest at 24 h post-injection((1.80±0.18) %ID/g). There were significant differences of T/NT ratios among different groups(F=4.776, P<0.05)and between different time points(F=8.630, P<0.05). Compared with negative control group (Na131I), the T/NT ratios significantly increased in 131I-PAMAM(G5.0)-SR group at 4, 8 and 24 h post-injection (t=4.169, 7.123 and 4.032, all P<0.05) and in 131I-PAMAM(G5.0)-GP group at 4 h post-injection (t=5.893, P<0.05). The T/NT ratio in 131I-PAMAM(G5.0)-SR group was higher than that in 131I-PAMAM(G5.0)-GP group at 24 h post-injection (t=2.871, P<0.05).@*Conclusions@#PAMAM(G5.0)-SR, PAMAM(G5.0)-GP and PAMAM(G5.0)-SR/GP can target the MTC models. 131I-PAMAM(G5.0)-SR has the best biological properties and may provide a new precision method for MTC diagnosis, treatment and prognosis evaluation.

Environment-responsive fluorescence probes in image-guided surgery / 中华核医学与分子影像杂志

Unlike conventional imaging technologies, fluorescent imaging benefits from its safety, high-spatial resolution and real-time capability, which make it a highly adoptable imaging method for tumor detection and image-guided surgery in clinics. There are two types of fluorescent probes, including always-on type and environment-responsive type, wherein environment-responsive probes are preferred due to higher target-to-background ratios, which can improve sensitivity and specificity. The environment-responsive probes include enzyme-reactive probes, pH-sensitive probes and hypoxia responsive probes. This review summarizes recent progress in environment-responsive probes, and discusses their potentials in tumor detection and image-guided surgery.

Targeting peptide-mediated 131I-polyamidoamine in medullary thyroid carcinoma bearing mice / 中华核医学与分子影像杂志

Objective To construct 131 I-the fifth generation polyamidoamine (PAMAM(G5.0)) with targeting peptide Ser-Arg-Glu-Ser-Pro-His-Pro (SRESPHP;SR) or Gly-Pro-Leu-Pro-Leu-Arg (GPLPLR;GP) and double targeting peptide SR/GP,and evaluate the targeting ability in medullary thyroid carcinoma (MTC) model.Methods PAMAM(GS.0),PAMAM(GS.0)-SR,PAMAM(GS.0)-GP and PAMAM(GS.0)-SR/GP were radiolabeled with 131I by chloramine T method.The radiolabeled yield and radiochemical purity were determined by thin layer chromatography.MTC xenografts were developed and the percentage radio-activity of injection dose per gram of tissue (％ID/g) in tumor and organs was measured at 24 h post-injection.Region of interest (ROI) was drawn and the tumor/non-tumor (T/NT) ratios at 4,8 and 24 h post-injection were calculated and compared among different groups.One-way analysis of variance,repetitive measurement analysis of variance and Dunnett-t test were used to compare the data of different groups.The relationship between ％ID/g and T/NT was analyzed with Pearson correlation.Results The radiolabeled yield was more than 75％ and radiochemistry purity was more than 90％.The difference of ％lD/g at 24 h post-injection was significant (F=14.400,P＜0.001) in tumors of all groups.The radioactive uptake in tumor of 131I-PAMAM (G5.0)-SR group was the highest at 24 h post-injection ((1.80± 0.18) ％ID/g).There were significant differences of T/NT ratios among different groups (F =4.776,P＜ 0.05)and between different time points (F =8.630,P＜0.05).Compared with negative control group (Na131 I),the T/NT ratios significantly increased in 131I-PAMAM(G5.0)-SR group at 4,8 and 24 h post-injection (t=4.169,7.123 and 4.032,all P＜0.05) and in 131I-PAMAM(G5.0)-GP group at 4 h post-injection (t =5.893,P＜0.05).The T/NT ratio in 131I-PAMAM (G5.0)-SR group was higher than that in 131 I-PAMAM (G5.0)-GP group at 24 h post-injection (t=2.871,P＜0.05).Conclusions PAMAM(G5.0)-SR,PAMAM(G5.0)-GP and PAMAM(G5.0)-SR/GP can target the MTC models.131I-PAMAM(G5.0)-SR has the best biological properties and may provide a new precision method for MTC diagnosis,treatment and prognosis evaluation.

Strand displacement-based molecular probe for high-specificity detection of microRNA / 中华检验医学杂志

Objective@#A new type of molecular probe design method was established to improve the sensitivity and specificity of microRNA detection. @*Methods@#This is an experimental study. The target hybridization sequence was designed on the stem side of the molecular beacon using the strand displacement principle and based on this, a new probe was designed by using the nucleic acid structure analysis software DNAman to optimize the secondary structure of the molecular probe, which was called as strand displacement molecular probe (MB-D) and MB-D plus. Taking microRNA-21 as an example, microRNA-21 and its related single nucleotide mutations were detected using conventional molecular probe (MB-C) and redesigned MBs (MB-D and MB-D plus) to analyze the differences on minimum detection limit, repeatability and specificity for microRNA detection among these three probes. @*Results@#The minimum detection limit of MB-C for microRNA-21 was 1 nmol/L, and the minimum detection limits for MB-D and MB-D plus were 0.1 nmol/L and 0.01 nmol/L, respectively. The established MB-D plus can significantly distinguish between miR-21 and single nucleotide mutations. @*Conclusion@#The molecular probe based on the principle of strand displacement and optimized by secondary structure can significantly increase the sensitivity and specificity of the probe for microRNA detection.(Chin J Lab Med, 2018, 41: 541-546)

Synthesis and optical characteristics of near infrared-Ⅱ fluorescent molecule CH1055 / 国际药学研究杂志

Objective To optimize the synthetic method for the fluorescent molecule CH1055 and perform a preliminary study on its water solubility and optical properties. Methods Starting from triphenylamine and benzothiadiazole, the desired products were synthesized via a series of reactions, such as Vilsmeier-Haack reaction, acylation, catalytic hydrogenation, bromination, condensation, silylation protection, Suzuki coupling, nitrification and reduction. The structures of the intermediates and targeted compound were confirmed by MS and1 H NMR. At the same time, the key reaction steps were optimized, and the solubility and optical properties of CH1055 were investigated both in vitro and in vivo. Results After improvement of the synthetic method, the total yield increased from 9.13％ in the literature to 12.1％ in the present study. The PEGylated product improved water solubility by about 300 times. At the wavelength of 750 nm long excitation light, CH1055 had better imaging characteristics than the traditional Cy5.5. Conclusion The present method for the CH1055 synthesis has appeared to be cheaper in cost, easy to operate, and higher in yield. After PEGylation modification, the water solubility of the target compound was greatly improved, which was highly advantageous to the development of a water-soluble NIR-Ⅱ fluorescent molecule. CH1055 showed excellent imaging properties in the long wavelength range, which implicated a new potential application of the fluorescent molecule.

Research progress in imaging agents targeting Aβ and Tau protein in Alzheimer's disease / 中华核医学与分子影像杂志

Alzheimer's disease (AD) is a neurodegenerative disease,which is insidious onset and progressive.The pathological features of AD include senile plaques composed of amyloid β (Aβ) and neurofibrillary tangles composed of Tau protein.Aβ and Tau protein targeted imaging agents,which make a non-invasive and high specificity diagnosis,might be useful for early diagnosis,efficacy monitoring and drug evaluation for AD.This review summarizes the progress and clinical applications of those agents in AD.

Research progress of positron-emitting molecular imaging probes for Alzheimer's disease / 中华核医学与分子影像杂志

As an advanced imaging technology,PET provides high sensitivity and accuracy for the diagnostic research of Alzheimer's disease (AD).Various pathophysiological information of AD can be illustrated by applying different molecular imaging probes.Three series of molecular imaging probes including glucose metabolism probes,neurotransmitter and neuroreceptor probes and neuropathological marker probes are introduced in this review.

Targeted Theranostic Nanoprobes for US/MRI Dual-mode Imaging and High Intensity Focused Ultrasound Synergistic Therapy:An in Vitro Experiment / 中国医学影像学杂志

Purpose To develop the folate-targeted theranostic nanoprobe, investigate the active targeting behavior of nanoprobes to hepatocellular carcinoma(HCC)in vitro,and discuss the effect of enhanced US/MRI dual-mode imaging in vitro and the synergistic effect of high intensity focused ultrasound on HCC killing. Materials and Methods The folate-targeted nanoprobe loaded with iron oxide nanoparticles (Fe3O4) and phase-shift material perfluorohexane (PFH) was prepared by double emulsion method and carbodiimide method. The average particle size, morphological structure and the ability of liquid-gas phase transition were detected. The active targeting ability of the nanoprobe to HCC BEL-7402 was observed in vitro.The ultrasonic imaging effect of nanoprobe was observed by HIFU irradiation in vitro.MRI was performed on the Fe3O4nanoprobe with different content of magnetic particles.The synergistic killing ability of the nanoprobe combined with HIFU on liver cancer cells was detected with in vitro apoptosis experiment. Results The folate-targeted nanoprobe loading iron oxide nanoparticles (Fe3O4) and phase-shift material PFH was prepared, with the average size of (402.50±66.43) nm. It was in the shape of regular sphere with the magnetic particle Fe3O4scattered inside. The HIFU irradiation caused liquid and gas phase transition.In vitro targeting experiments showed that BEL-7402 cells were surrounded by a large number of nanoscale probes.In vitro dual mode imaging showed that the ultrasonic echo intensity was obviously enhanced after HIFU irradiates nanoscale probes. The MR negative imaging ability of the nanoprobe was also enhanced with the enhancement of Fe3O4concentration in nanoparticles. In vitro apoptosis experiments showed that the nanoscale probe had the ability to significantly enhance the effect of HIFU on the killing of HCC. Conclusion The prepared folate-targeted theranostic nanoprobes exhibit the excellent capability for in vitro targeting.They can be used for ultrasound and MRI as multimodal imaging agents and coordinates with HIFU to enhance the effect on killing HCC, which realizes the early diagnosis of tumor and targeted precision therapy.

Advances in application of environment-responsive smart probes in tumor therapy / 肿瘤

With the development of medical nanotechnology, scientists have found that nanoparticle drug delivery system can improve the accumulation of anti-tumor drugs inside the tumor and reduce the damage to normal tissues, so as to increase the treatment effect while decrease its side effect. In recent years, the nanoparticle drug delivery system has been gradually developing towards intellectualization, and various smart probes which are stimuli-responsive and sensitive to microenvironment of tumor have been designed. Those probes can be divided into two categories: internal (including pH, enzyme, and redox) and external (including light, temperature, ultrasound, and magnetic field) environment-responsive probes. In this paper, the latest research progress in the two kinds of environment-responsive smart probes in the field of tumor therapy is reviewed, and the further research direction is also prospected.

Mujeres inmigrantes y tamizaje de cáncer cervical en un centro ginecológico privado de Quito - Ecuador / Immigrant women and cervical cancer screening in a private gynecology center in Quito - Ecuador

Objetivo: las mujeres inmigrantes enfrentan problemas para acceder a programas de salud, en relación al tamizaje del cáncer cervical y su prevención. Estudios demuestran que mientras más reciente es la migración (<10 años), es menos probable la realización de exámenes para detectar cáncer cervical. Se plantea la hipótesis de que las mujeres inmigrantes tendrán índices menores de tamizaje de lesiones cervicales causadas por el virus del papiloma humano (HPV) comparadas con las mujeres ecuatorianas. Métodos: se realizó un estudio observacional en 113 mujeres de 17 a 55 años de edad: 56 mujeres inmigrantes/refugiadas y 57 mujeres ecuatorianas Se usó citología cérvico-vaginal y una prueba de detección de ADN del HPV basada en Captura Híbrida II. Las participantes fueron reclutadas mediante selección no probabilística (desde mayo 2014 hasta junio 2015). Las mujeres ecuatorianas fueron incluidas por solicitud voluntaria una vez que recibieron toda la información del proceso; mientras que las mujeres inmigrantes se incluyeron mediante información gráfica y entrevistas, lográndose alianzas entre organizaciones comunitarias dedicadas a ayudarlas y proveedores médicos privados. Resultados: tanto las ecuatorianas (14.15%, n=16) como las inmigrantes (5.3%, n=6) que nunca se realizaron un examen de citología, presentan resultados positivos en el examen de ADN-HPV (alto o bajo riesgo). Las ecuatorianas acceden a la citología cérvico-vaginal, independientemente de su edad, mientas que las mujeres inmigrantes menores de 30 años no han conseguido, hasta el momento del estudio, acceder a este servicio (p < 0.05). Conclusiones: existe una diferencia significativa en los índices de tamizaje de cáncer cervical entre los grupos de inmigrantes /refugiadas y residentes, de acuerdo al lugar de nacimiento y la duración de su estadía en Ecuador.

Objective: immigrant women face health problems and challenges to access health care, no matter what destination country they choose. Regarding cervical cancer screening and prevention, migrant women access to a health care programme is an important issue. Some studies have shown that while migration is recent (under 10 years), is less likely to get cervical cancer examination services comparing with non-immigrant women. The hypothesis stated that immigrant women would have lower rates of screening and a higher prevalence of HPV related lesions, compared to those women from Ecuador. Methods: a 12 months period study was performed including 113 women age 17 to 55, split into two groups: 56 migrant/refugee and 57 Ecuadorian residents, using cervical cytology and a DNA for HPV test based on hybrid capture II. Agreements between community organizations and private providers were reached to help the groups. Results: both groups, Ecuadorian women (14.15%, n=16) and immigrant women (5.3%, n=6) that never had a Papanicolaou test, have HPV-DNA test positive for high and low risk types. Ecuadorian residents have access to cervical cytology regardless their age, while immigrant/refugee women under 30 years have not access to the test, the difference is statistically significant. Conclusions: there is a significant difference in screening levels for cervical cancer between immigrant/refugee women according to place of origin and duration of stay in Ecuador.

Clinical value of fluorescence in situ hybridization positive of exfoliated urothelial cells in urothelial carcinoma / 北京大学学报(医学版)

Objective: To analyze the clinical pathologic characteristics of cases with fluorescence in situ hybridization (FISH) positive of exfoliated urothelial cells, so as to evaluate the clinical utility of FISH in the diagnosis of urothelial carcinoma (UC).Methods: A total of 271 cases of FISH positive in Department of Urology of Peking University First Hospital from Apr.2012 to Sep.2015 were recruited in this study.Retrospective analysis was made on their clinical data.For FISH analysis, labeled probes specific for chromosomes 3, 7, 17, and the p16 (9p21) gene were used to assess chromosomal abnormalities indicative of malignancy.The positive predict values (PPV) of all the techniques were analyzed.Results: Of the 271 patients, 207 cases were UC, 7 cases were non-UC, and 57 cases were benign diseases.The PPV of FISH in detecting UC was 76.4%, while the 95% confidence interval (CI) 71.3% to 81.5%.In the cohort of FISH positive, this value was similar to that of urinary cytology (PPV 86.8%, 95% CI: 78.5%-95.0%).The PPV of FISH was lower than that of cystoscopy and ureteroscopy (PPV 96.1%, 95% CI: 91.7%-100.0%).There were significant differences between this study and the PPV of FISH reported abroad (PPV 53.9%, χ2=33.048, P<0.001).Of all the UC with FISH positive, bladder cancer showed an earlier pathological stage versus renal pelvic carcinoma and ureteral carcinoma, with significance (χ2=5.894, P=0.015, and χ2=13.601, P<0.001, respectively).However, no difference was found in the size, pathological stage and pathological grade of tumors between the urinary cytology positive group and the urinary cytology negative group.The rate of high-grade UC in ureteral carcinoma of FISH positive was 92.3%, much higher than that of ureteral carcinoma reported domestically.Conclusion: The PPV of FISH in detecting UC is higher relatively, with a better clinic value for Chinese patients.The ureteral carcinoma with FISH positive obtains a higher pathological grade, which is of great guiding significance for UC.

Recent advances in radiotracers for apoptosis imaging / 中华核医学与分子影像杂志

Apoptosis plays a crucial role in various physiology and pathologic processes of organisms.The non-invasive imaging of apoptosis may have potentially important diagnostic and prognostic predictive values on apoptosis-associated diseases, such as neurodegenerative diseases and neoplasms.Molecular imaging of nuclear medicine provides a useful tool to investigate these features in vivo by using suitable radiopharmaceuticals.This review summarizes the recent advances in imaging agents targeting the apoptosis process.

Preparation of folate-NOTA-Al18F targeting folate receptor and its microPET/CT imaging / 中华核医学与分子影像杂志

Objective To prepare PET molecular probe folate-NOTA-Al18F(18F-FNA) and to explore its feasibility as an imaging agent in folate receptor positive KB tumor.Methods 18F-FNA was prepared by the method of aluminum fluoride coordination labeling, and the effect of phase transfer catalyst K2.2.2 on the labeling yield was evaluated.Biological distribution was carried out at 10, 30 and 90 min after injection of 3.7 MBq 18F-FNA in nude mice (n=20) xenografted with KB tumor, and the radioactive uptake (%ID/g) and T/NT ratios were then calculated in different organs or tissues.MicroPET imaging was performed at 40 min after injection of 18F-FNA (3.7 MBq).Results The labeling yield of 18F-FNA increased with the presence of K2.2.2.The radiochemical yield was above 98%.The radiochemical purity was above 99%, and still above 98% after maintained in PBS and FBS at 37 ℃ for 4 h.The biodistribution showed that the blood clearance of the probe was slow, and the uptakes in kidneys and tumor which overexpressed folate receptor were significantly high ((5.12±0.58) %ID/g and (1.37±0.20) %ID/g).The high radioactive uptake was observed in KB xenografted mice using microPET imaging.Conclusions The labeling yield of 18F-FNA could increase with the presence of K2.2.2.Furthermore, the encouraging biological distribution and microPET imaging results indicate that 18F-FNA may be a candidate for PET imaging in targeting folate receptor.

Application of PET probes in Alzheimer's disease / 军事医学

Alzheimer's disease (AD) is the most common type of dementi a.PET probes can specifically detect the in vivo amyloid β peptide(Aβ) and Tau protein in AD inpatients' brain.The application of PET probes in AD is important for its early diagnosis and early intervention.US FDA has approved three PET probes for Aβ imaging while probes for Tau are still under research and development.This review summarizes current development of Aβ and Tau PET probes used for AD.

Preliminary research on functional polymer liposome-entrapped gold nanoparticles as CT contrast agents / 中国生化药物杂志

Objective To research the functional polymer liposome-trapped gold nanoparticles as molecular probes used as CT contrast agents.Methods Gold nanoparticles were entrapped by ultrasonic micro-emulsion method using self-developed linoleic acid-modified dextran polymer liposome.Under the same concentrations,clinical imaging was performed with Iohexol as control for the analysis of CT value differences.Then,the particle suspensions at appropriate concentration(6 mg/mL)were intravenously injected into Balb/c nude mice for real-time observation of CT imaging.ResultsIn vitro results showed that nanoparticles at greater than 4 mg/mL could present much higher CT value than Iohexol at the same conditions,while in vivo studies indicated nanoparticles could clearly show different organ contrast with prolonged circulation time.Conclusion Compared to clinical contrast agent Iohexol,functional polymer liposome entrapped gold nanoparticles could possess a great application prospect to be used as a new type of molecular probes for CT enhanced imaging.

Albumin-based SPECT/Photoacoustic Dual-modality Nanoprobe in Liver Imaging / 中国医学影像学杂志

Purpose Liver fibrosis,liver cirrhosis and liver cancerseriously threaten human health.To detect liver diseases by specific nanoprobes,and to provide reference for the formulation of treatment strategies.Materials and Methods In this study,bovine serum albumin was used as a skeleton and modified with galactose groups for targeting asialoglycoproteinreceptors on liver.The albumin was labeled with radioactive iodine by chloramines T method,and indocyanine green molecules was encapsulated to form liver-targeting nanoparticles.Physical and chemical characterization (particle size and spectral characterization),bio-distribution,SPECT imaging and photoacoustic imaging were carried out respectively.Results The size of the nanoparticles was about 86.4 nm and there were two obvious absorption peaks at 705 nm and 780 nm.Bio-distribution showed that the radiolabeled nanoparticles had a high distribution in liver at 60 min [(55.52 ± 5.39)％ID/g],while after the receptor was inhibited,the uptake in liver was reduced to (37.01 ± 7.38)％ID/g,indicating a significant inhibitory effect (P＜0.05);the uptake of this material at 240nm still remained (34.22±4.44)％ID/g,while in other organs,the detected uptake was quite low,with a statistically significant difference (P＜0.05).The results of SPECT and photoacoustic imaging were consistent with the data of bio-distribution,and images showed highest signal on liver.Thus,the probe was suitable for liver imaging.Conclusion 131I-labeled albumin nanoparticle is an excellent liver-targeting dual modal imaging probe,which can be used for the detection of liver diseases.

MUC1 Mucin 1 Antibody Marked Superparamagnetic Iron Oxide Nanoparticles in Nude Mice Model of Pancreatic Cancer: An Experimental Study / 中国医学影像学杂志

Purpose To prepare superparamagnetic iron oxide nanoparticles (SPION) probe targeted and modified by MUC1 murin (MUC1) in order to explore its MRI characteristics in pancreatic cancer transplantation model.Materials and Methods Chemical conjugate method was adopted for coupled response of MUC1 and SPION to construct targeted probe and tested its basic physical properties,including water and diameter,surface charge and MR signal measuring.Meanwhile,nude mice model of pancreatic cancer transplant subcutaneous sarcoma was set up to study imaging effect inside the nude mice.Transplant sarcoma specimen was taken and immunohistochemical and Western blot were adopted to measure MUC1 expression.Results Partial size of the prepared particle probe was approximately 63.5 nm and surface charge was about 10.2 mV.The probe solution could obviously decrease MR transverse relaxation time (T2 value).In vitro experiment,MUC 1 could selectively gather on nude mice transplant sarcoma model could greatly lower T2 signal intensity.Conclusion Prepared probe has small partial size,superparamagnetic and other advantages.It can realize combination with pancreatic cancer tissue specificity and provide reliable in vivo iconology in early stage for disease diagnosis through vitro imaging.