1,720,989 research outputs found
Myocardial positron emission tomography/computed tomography scan revealing right coronary artery involvement in large vessel vasculitis
Full text linkDescription of coronary artery involvement in a patient with Takayasu arteritis detected using a PET/CT perfusion scan in a symptomatic patient with normal coronary angiography
A Specific HPLC Method to Determine Residual HEPES in [(68)Ga]Ga-Radiopharmaceuticals: Development and Validation
No full textBackground: Nowadays, in Nuclear Medicine, clinically applied radiopharmaceuticals must meet quality release criteria such as high radiochemical purity and radiochemical yield. Many radiopharmaceuticals do not have marketing authorization and have no dedicated monograph within European Pharmacopeia (Ph. Eur.); therefore, general monographs on quality controls (QCs) have to be applied for clinical application. These criteria require standardization and validation in labeling and preparation, including quality controls measurements, according to well defined standard operation procedures. However, QC measurements are often based on detection techniques that are specific to a certain chromatographic system. Several radiosyntheses of [(68)Ga]Ga-radiopharmaceuticals are more efficient and robust when they are performed with 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) buffer, which is considered as an impurity to be assessed in the QC procedure, prior to clinical use. Thus, Ph. Eur. has introduced a thin-layer chromatography (TLC) method to quantify the HEPES amount that is present in [(68)Ga]Ga-radiopharmaceuticals. However, this is only qualitative and has proven to be unreliable. Here we develop and validate a new high-performance liquid chromatography (UV-Radio-HPLC) method to quantify the residual amount of HEPES in (68)Ga-based radiopharmaceuticals. Method: To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document that was adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. A range of concentrations of HEPES (100, 80, 60, 40, 20, 10, 5, 3 μg/mL) were analyzed. Moreover, to test the validity and pertinence of our new HPLC method, we analyzed samples of [(68)Ga]Ga-DOTATOC; [(68)Ga]Ga-PSMA; [(68)Ga]Ga-DOTATATE; [(68)Ga]Ga-Pentixafor; and [(68)Ga]Ga-NODAGA-Exendin-4 from different batches that were prepared for clinical use. Results: In the assessed samples, HEPES could not be detected by the TLC method that was described in Ph. Eur. within 4 min incubation in an iodine-saturated chamber. Our developed HPLC method showed excellent linearity between 3 and 100 μg/mL for HEPES, with a correlation coefficient (R(2)) for calibration curves that was equal to 0.999, coefficients of variation (CV%) < 2%, and percent deviation value of bias from 100% to 5%, in accordance with acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed and the limit-of-quantification (LOQ) was 3 μg/mL, confirming the high sensitivity of the method. The amount of HEPES that was detected with our developed HPLC method in the tested [(68)Ga]Ga-radiopharmaceuticals resulted well below the Ph. Eur. limit, especially for [(68)Ga]Ga-NODAGA-Exendin-4. Conclusions: The TLC method that is described in Ph. Eur. to assess residual HEPES in [(68)Ga]-based radiopharmaceuticals may not be sufficiently sensitive and thus unsuitable for QC release. Our new HPLC method was sensitive, quantitative, reproducible, and rapid for QCs, allowing us to exactly determine the residual HEPES amount in [(68)Ga]Ga-radiopharmaceuticals for safe patient administration
A Rapid and Specific HPLC Method to Determine Chemical and Radiochemical Purity of [68Ga] Ga-DOTA-Pentixafor (PET) Tracer: Development and Validation
No full textBACKGROUND: Due to its overexpression in a variety of tumor types, the chemokine receptor 4 (CXCR4) represents a highly relevant diagnostic and therapeutic target in nuclear oncology. Recently, [68Ga]Ga-DOTA-Pentixafor has emerged as an excellent imaging agent for positron emission tomography (PET) of CXCR4 expression in vivo. Preparation conditions may influence the quality and in vivo behaviour of this tracer and no standard procedure for the quality controls (QCs) is available.OBJECTIVE: The developed analytical test method was validated because a specific monograph in the Pharmacopoeia is not available for [68Ga]Ga-DOTA-Pentixafor.METHODS: A stepwise approach was used, based on the quality by design (QbD) concept of the ICH Q2 (R1) and Q8 (Pharmaceutical Development) guidelines in accordance with the regulations and requirements of EANM, SNM, IAEA and WHO.RESULTS: The purity and quality of the radiopharmaceutical obtained according to the proposed method resulted high enough to safely administrate it to patients. Excellent linearity was found between 0.5 and 4 mug/mL, with a correlation coefficient (r2 ) for calibration curves equal to 0.999, average coefficient of variation (CV%) < 2% and average bias% that doesn't deviate more than 5% for all concentrations.CONCLUSION: This study developed a new rapid and simple HPLC method of analysis for the routine QCs of [68Ga]GaDOTA-Pentixafor to guarantee the high quality of the finished product before release
Preoperatory imaging evaluation in primary hyperparathyroidism and associated thyroid disease
No full textPrimary hyperparathyroidism (pHPT) is an endocrinological disorder characterized by excessive secretion of parathormone. Minimally invasive approach has become a widespread surgical method for pHPT treatment due to the improvement of preoperative gland localization imaging techniques and the use of intraoperative PTH dosage (IOPTH). We discuss the results of different imaging technique
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Primary Large Cell Neuroendocrine Carcinoma of the Mediastinum
No full textBACKGROUND: to present a rare case of primary neuroendocrine carcinoma of the mediastinum treated by multimodal therapy.
METHODS: a 50-year-old man, non-smoker, with unremarkable past medical history, presented for asthenia, dyspnea and sub-sternal discomfort. A chest CT-scan showed a huge mass of 10,7x5,5x9,5cm in the anterosuperior mediastinum. The mass seems infiltrate both brachiocephalic veins, the superior vena cava, pericardium and both lungs (Fig.1a/b).
PET-CT showed an intense hyperactivity of the mediastinal mass. CT-guided needle biopsy allows diagnosis of neuroendocrine carcinoma. After multisciplinary discussion, a multimodal approach was planned. The patient underwent 4 cycles of chemotherapy with cisplatin and gemcitabine. Since chest CT-scan showed a reduction of the tumor (7,4x5,6x9cm), a surgical resection was proposed.
RESULTS: a median sternotomy was performed. On exploration, both lungs were marginally infiltrated. The pericardium was partially excised; the left anonymous vein was almost totally invaded by the tumor. The right anonymous vein was infiltrated at the confluence with the superior vena cava. After total caval clamping (clamping time: 27’), a partial section and reconstruction with bovine pericardium was performed (Fig.1c). The patient was discharged uneventfully on postoperative-day 9. The patient underwent 25 sessions of adjuvant radiotherapy. Currently, he’s free of disease after 30 months. Macroscopically the mass measured 9x8x3cm, looks whitish with tense-elastic consistency. Microscopically it showed clusters of small uniform cells, sometimes with cuboidal morphology, with nuclear pleomorphism and small nucleoli, arranged in trabeculae, nests and lobules and immersed in a hyaline stroma with foci of necrosis (Fig.2a). Perineural and vascular invasion were present. Immunohistochemistry showed the tumor cells were positive for chromogranin (Fig.2c), synaptophysin (Fig.2d), cytokeratins and negative for TTF1, FAP, PSA. The proliferation index Ki-67 was 10% (Fig.2b). Considering the radiological, morphological and immunophenotypic characteristics, the diagnosis was consistent with primary neuroendocrine carcinoma of the mediastinum.
CONCLUSIONS: mid-term survival was achieved after aggressive multimodal therapy
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