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Daviskas E.,11 West Royal Prince Hospital | Anderson S.D.,11 West Royal Prince Hospital | Eberl S.,PET and Nuclear Medicine | Young I.H.,11 West Royal Prince Hospital
Respiratory Medicine | Year: 2010

Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance (MCC) leading to mucus plugs, and airway obstruction. Inhaled mannitol improves mucus clearance in other hypersecretory diseases. This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction. Seven stable asthmatics, age 52 ± 20 yr, lifelong non-smokers, without the diagnosis of bronchiectasis, with chronic cough and sputum production, treated with inhaled corticosteroids participated in the study. MCC and cough clearance (CC) was measured on 4 visits: at baseline (no cough or mannitol), with mannitol (240 and 480 mg) and cough control (no mannitol) over total 90 min using a radioaerosol technique and imaging with a gamma camera. Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min. Premedication with eformoterol (12 μg) on all visits protected all subjects from bronchoconstriction (fall in FEV1 > 15%) in response to mannitol. Mean (±SD) clearance over 60 min increased from 5.5 ± 5.6% at baseline and 7.3 ± 6.6% with cough control to 19.5 ± 14.6% and 26.4 ± 11.5% with 240 mg (p < 0.003) and 480 mg (p < 0.0001) of mannitol respectively. Total clearance (MCC + CC) over 90 min increased from 6.9 ± 6.5% (baseline) and 12.6 ± 8.3% without mannitol (cough control) to 34.6 ± 13.5 and 36.6 ± 10.4% with 240 and 480 mg mannitol respectively (p < 0.0001). Clearance over 90 min at baseline was not significantly different to cough control (p > 0.05). Mannitol improved clearance in all lung regions (p < 0.005). In conclusion, mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance. Clinical Trial registered with www.anzctr.org.au; Number ACTRN 12609001066279.aspx. © 2010 Elsevier Ltd. All rights reserved.

Scharli R.K.,RAPID PET Labs. | Scharli R.K.,University of Western Australia | Price R.I.,RAPID PET Labs. | Price R.I.,University of Western Australia | And 12 more authors.
AIP Conference Proceedings | Year: 2012

A semi-automated, in-house external beamline, ≤40 μA at 11.7 MeV for 120 min (degraded from 18 MeV to suppress 88Y & 88Zr co-production) produced 89Zr from 89Y(p,n)89Zr. EOB activity (by HPGe γ-spectr.) of 89Zr in target discs, derived from multiple runs, was 1.42 GBq (±0.45 GBq [SD], n=4) which was 67% (±21%, n=4) of the theoretical activity, with a maximum of 1.84 GBq (87% of theory) achieved. Recovery was 88% (±9%, n=4), radionuclidic purity >99% (n=4) and chemical purity 0.2 ppm Zr (±0.3 ppm, n=3, ICP-MS). The Zr:Y ratio improved from 1:10000 in the pre-filtered solution to 1:10 in the product purified by hydroxamate column. Efficiency of radiolabeling to monoclonal antibody (mAb; trastuzumab) was 100% and purified 89Zr did not bind non-specifically to mAb. Chelator:mAb ratio was 1.3:1. No-carrier-added specific activity of purified 89Zr was 408 MBq/μg (±26 MBq/μg, n=2) via the titration-by-chelator method. Minimum ligand concentration for which 100% labeling occurred was 302 nmol/L. Small animal PET imaging (Philips Mosaic; scan acquisition time 10 min; decay & randoms corrected; image reconstructed using a 3-D RAMLA algorithm) demonstrated marked tumor-specific uptake of 89Zr-labeled mAb but nil 'free' 89Zr (as chloride) tumor uptake. © 2012 American Institute of Physics.

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