Radiolabeling, biodistribution and gamma scintigraphy of noscapine hydrochloride in normal and polycystic ovary induced rats

<p>Abstract</p> <p>Background</p> <p>Noscapine, an alkaloid from <it>Papaver somniferum</it>, widely used as an antitussive, is being clinically studied in the treatment of polycystic ovary syndrome (PCOS) and a few other cancers primarily because of its anti-angiogenesis properties. With the advent of diverse application of noscapine, we sought to determine whether the radiolabeling method can be useful in studying uptake and kinetics of the molecule in-vivo. Specific objectives of this study were to radiolabel noscapine with Technetium-99m (Tc-99m), to determine its organ biodistribution in rat model and study its uptake kinetics in PCOS model.</p> <p>Methods</p> <p>A method for radiolabeling noscapine with Tc-99m was standardized using stannous reduction method and its in vitro and in vivo stability parameters were studied. The radiopharmaceutical was also evaluated for blood kinetics and biodistribution profile. An animal model of PCOS was created by using antiprogesterone RU486 and uptake of ^99mTc-noscapine in normal and PCOS ovaries was compared using gamma scintigraphy.</p> <p>Results</p> <p>Noscapine hydrochloride was successfully radiolabeled with Tc-99m with high labeling efficiency and in vitro stability. Most of the blood clearance of the drug (80%) took place in first hour after intravascular injection with maximum accumulation being observed in liver, spleen, kidney followed by the ovary. At 4 hours post injection, radiolabeled complex accumulation doubled in PCOS ovaries in rats (0.9 ± 0.03% ID/whole organ) compared to normal cyclic rats (0.53 ± 0.01% ID/whole organ). This observation was further strengthened by scintigraphic images of rats taken at different time intervals (1 h, 2 h, 4 h, and 24 h) where SPECT images suggested discrete accumulation in the PCOS ovaries.</p> <p>Conclusion</p> <p>Through our study we report direct radiolabeling of noscapine and its biodistribution in various organs and specific uptake in PCOS that may show its utility for imaging ovarian pathology. The increased ovarian uptake in PCOS may be related to its receptor binding suggesting possible role of ^99mTc-noscapine in PCOS diagnostics and therapeutics.</p

Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM) study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS). The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.O objetivo deste trabalho foi planejar microemulsão/mucoaesiva em gel a fim de melhorar a captação cerebral de ibuprofeno por via intranasal. A microemulsão para mucoadesão com ibuprofeno (MMEI) foi desenvolvida pela incorporação de policarbofil como polímero mucoadesivo em microemulsão otimizada (MEI) com base em Capmul (MCM) e foi submetida à caracterização, estabilidade, mucoadesão e naso-ciliotoxicidade. A captação cerebral de ibuprofeno pela via nasal foi estudada por meio de estudo de biodistribuição em ratos albinos suíços. MEI se mostrou transparente, estável e não ciliotóxica, com 66,29 ± 4,15 nm, -20,9 ± 3,98 mV e 98,66 ± 1,01%, respectivamente, de tamanho médio dos glóbulos, potencial zeta e conteúdo do fármaco. O estudo revelou o estreita distribuição do tamanho dos glóbulos de MEI. Após administração intranasal única de MMEI e MEI, em dose de 2,86 mg/kg, a captação de ibuprofeno no bulbo olfativo foi em torno de 3,0 e 1,7 vezes maior, comparativamente, à injeção endovenosa de ibuprofeno (IDS). As taxas de ASC em tecido cerebral em relação ao plasma, obtidas após administração da MMEI nasal, foram, significativamente, mais elevadas do que aquelas observadas após a administração intravenosa de IDS. Os resultados do presente estudo mostraram que a microemulsão/mucoadesiva em gel poderia ser uma abordagem promissora para o direcionamento cerebral de ibuprofeno por via intranasal

PRELIMINARY EVALUATION OF AN ANTHRAQUINONE CONJUGATED DOTA DERIVATIVE AS SPECT AGENT

Objective: An anthraquinone derivative, DO3A-Act-AQ having DO3A (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-trisacetic acid) scaffold is radio labeled with 99mTc radioisotope and evaluated as a SPECT imaging agent for tumor.Methods: Preliminary in-vivo evaluation of 99mTc-DO3A-Act-AQ radioconjugate including blood kinetics, biodistribution and gamma scintigraphic imaging is performed on BMG-1 tumor xenografted mice after successful optimization of the radiolabeling condition.Results: The radiotracer, 99mTc-DO3A-Act-AQ was produced in high radiochemical yield of&gt;96% and specific activity of 3.62 MBq/nmol at pH 7.5 and 150 µg stannous chloride. Radioconjugate displayed excellent in-vitro and in-vivo stability with only ~2% transchelation of radiometal at 24 h p. i and rapid blood clearance from the system with t1/2(F) = 38.04±0.35 min and t1/2(S) = 5 h 30 min±0.67. Significant tumor-to-muscle ratio of&gt;7 at 2 h p. i. in biodistribution and SPECT imaging studies in BMG-1 tumor xenografted mice suggested the tumor specificity of the radioconjugate.Conclusion: Stable radiocomplex formation of 99mTc-DO3A-Act-AQ and its significant tumor specificity demonstrated its future application as a promising SPECT radioligand for tumor imaging

Echocardiography of isolated subacute left heart tamponade in a patient with cor pulmonale and circumferential pericardial effusion

Patients with advanced idiopathic pulmonary artery hypertension have often a chronic pericardial effusion. It is the result of increased transudation and impaired re-absorption due to elevated venous pressure. These patients have pre-existent symptoms and signs of chronic right heart failure. High degree of suspicion is required to detect of development of an atypical form of tamponade with isolated compression of left heart chambers as shown in present case report. Transthoracic echocardiography provides a rapid access to the correct diagnosis, a prompt relief of symptoms following the ultrasound guided pericardiocentesis and important diagnostic tool for regular follow up of patients thereafter as shown in our case report

How to Interpret a Functional or Motility Test - Sphincter of Oddi Manometry

To date, endoscopic manometry is the best method for evaluating the function of the sphincter. Sphincter of Oddi manometry (SOM) remains the gold standard to correctly diagnose the sphincter of Oddi dysfunction (SOD) and stratify therapy. Several dynamic abnormalities relating to the intensity, frequency, and propagation of sphincter contractions have been described. However, their clinical use generally has been abandoned in favor of basal sphincter pressure alone, because this measurement is stable over time, and has stronger interobserver reliablility, reproducibility on repeating testing, and is associated with the responsiveness to therapy. A significant elevated risk of pancreatitis was attributed to the technique. The risk of pancreatitits associated with manometric evaluation of the pancreatic sphincter is markedly reduced when manometry is performed with continous aspiration from the pancreatic duct via one of the 3 catheter lumens. This section reviews indications, conscious sedative drugs, techniques, and the appropriate interpretations of SOM

Prospective randomized comparison of gastrotomy closure associating tunnel access and over-the-scope clip (OTSC) with two other methods in an experimental ex vivo setting

Background: Safe transgastric natural orifice transluminal endoscopic surgery (NOTES) procedures require a reliable closure of the gastrotomy. Recently a novel peritoneal access method via a submucosal tunnel has been described with encouraging preliminary results. Aim: The aim is to compare a submucosal tunnel access plus over-the-scope clip (OTSC) system for closure with two other closure modalities. Patients and methods: This is a prospective ex vivo study conducted on 42 porcine stomach models equally randomized into three groups in an academic medical center. The procedures performed in each group included: (1) Tunnel (6 cm) + endoclips; (2) Knife + balloon dilation access + OTSC; and (3) Tunnel + OTSC. A pressurized air-leak test was performed to evaluate the strength of the closure. Stomach volumes, procedure times, number of clips, and incision sizes were also registered. Results: The mean air-leak pressure was statistically higher in Group 3 than in Groups 1 and 2–95.2 ± 19.3 mmHg versus 72.5 ± 35.2 and 79.0 ± 24.5 mmHg (P < 0.05). The gastrotomy creation times for Groups 1, 2, and 3 were 28.0 ± 10.1, 4.3 ± 1.4, and 20.1 ± 10.6 minutes, respectively, with significantly lower time in Group 2 (P < 0.001). The closure times were 16.1 ± 6.1, 6.5 ± 1.2, and 5.3 ± 3.0 minutes, respectively, and significantly longer in the endoclip group (P < 0.001). There were no differences in the volumes and the incision sizes among the three groups. Conclusion: The combination of a submucosal tunnel access and OTSC offers a stronger closure than the other methods studied

A meta-analysis on efficacy and safety: single-balloon vs. double-balloon enteroscopy

Background and aim: Double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) are new techniques capable of providing deep enteroscopy. Results of individual studies comparing these techniques have not been able to identify a superior strategy. Our aim was to systematically pool all available studies to compare the efficacy and safety of DBE with SBE for evaluation of the small bowel. Methods: Databases were searched, including PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The main outcome measures were complete small-bowel visualization, diagnostic yield, therapeutic yield, and complication rate. Statistical analysis was performed using Review Manager (RevMan version 5.2). Meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. We used the χ2 and I2 test to assess heterogeneity between trials. Results were expressed as risk ratios (RR) or mean differences with 95% confidence intervals (CI). Results: Four prospective, randomized, controlled trials with a total of 375 patients were identified. DBE was superior to SBE for visualization of the entire small bowel [pooled RR = 0.37 (95% CI: 0.19–0.73; P = 0.004)]. DBE and SBE were similar in ability to provide diagnosis [pooled RR = 0.95 (95% CI: 0.77–1.17; P = 0.62)]. There was no significant difference between DBE and SBE in therapeutic yield [pooled RR = 0.78 (95% CI: 0.59–1.04; P = 0.09)] and complication rate [pooled RR = 1.08 (95% CI: 0.28–4.22); P = 0.91]. Conclusions: DBE was superior to SBE with regard to complete small bowel visualization. DBE was similar to SBE with regard to diagnostic yield, ability to provide treatment and complication rate, but these results should be interpreted with caution as they is based on very few studies and the overall quality of the evidence was rated as low to moderate, due to the small sample size

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

Pancreatic cancers are usually detected at an advanced stage and have poor prognosis. About one fifth of these arise from pancreatic cystic lesions. Yet not all lesions are precancerous, and imaging tools lack adequate accuracy for distinguishing precancerous from benign cysts. Therefore, decisions on surgical resection usually rely on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Unfortunately, cyst fluid often contains few cells, and fluid chemical analysis lacks accuracy, resulting in dire consequences, including unnecessary pancreatic surgery for benign cysts and the development of cancer. Here, we report an optical spectroscopic technique, based on a spatial gating fibre-optic probe, that predicts the malignant potential of pancreatic cystic lesions during routine diagnostic EUS-FNA procedures. In a double-blind prospective study in 25 patients, with 14 cysts measured in vivo and 13 postoperatively, the technique achieved an overall accuracy of 95%, with a 95%confidence interval of 78–99%, in cysts with definitive diagnosis