Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.
The radiosynthesis, as well as the in vivo and ex vivo biodistribution of the 11C radiolabelled 3‐(4,5‐diphenyl‐1,3‐oxazol‐2‐yl)propanal oxime (6, [11C]SZV 1287) are reported. SZV 1287 is a novel semicarbazide‐sensitive amine oxidase (SSAO) inhibitor and a promising candidate to be a novel analgesic for the treatment of neuropathic pain. Its radiolabelling was developed via a four‐step radiosynthesis which started from the reaction of a Grignard reagent with [11C]CO2 to produce [11C]oxaprozin (3). In the next step this carboxylic acid 3 was directly reduced to yield the corresponding aldehyde, which was then converted into the oxime. [11C]SZV 1287 was administered to male NMRI mice. The animals were examined with dynamic PET/MR imaging for 90 minutes. Biodistribution studies were performed at 10, 30, 60 and 120 minutes post injection. The accumulation of the labelled compound was observed in the brain of the animals. The main excretion pathway was found to be through the liver and intestines. These studies provide preliminary information for pharmacokinetic characterization of the SZV 1287.
SHFJV together with TIVA enlarges the diagnostic and therapeutic options in endoscopic surgery of the respiratory tract and is in many cases the precondition for endoscopic treatment without tracheotomy. In particular, the newly developed jet-tracheoscopes widen the spectrum of endoscopic surgery and allow the use of the micromanipulator guided CO2-laser in the trachea.
We report a case of an infant with spontaneous chylothorax due to the congenital malformation of a small lymph vessel of the chest wall. Conservative therapy with omitting long-chain fatty acids from the diet, fat-free nutrition, total parenteral nutrition and intravenous somatostatin did not result in the decrease of pleural effusion. Thoracic surgical intervention performing thoracic duct ligation and using fibrin sealants was applied after 10 days of unsuccessful conservative therapy, and resulted in the complete recovery of the patient. Our experience support the already existing observations, that in cases where the daily loss of chyle exceeds 100 ml per age years and/or lasts longer than 2 weeks, early surgical intervention is recommended.
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