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Abstract  The International GNSS Service (IGS) has been producing the total troposphere zenith path delay (ZPD) product that is based on combined ZPD contributions from several IGS Analysis Centers (AC) since GPS week 890 in 1997. A new approach to the production of the IGS ZPD has been proposed that replaces the direct combination of diverse ZPD products with point positioning estimates using the IGS Combined Final orbit and clock products. The new product was formally adopted in 2007 after several years of concurrent production with the legacy product. We describe here the advantages of the new approach for the IGS ZPD product, which enhance the value of the new ZPD product for climate studies. We also address the impact the IGS adoption in November 2006 of new GPS antenna phase center standards has had on the new ZPD product. Finally we describe plans to further enhance the ZPD products. [ABSTRACT FROM AUTHOR]

There has recently been increasing interest in the development of radioprobes that specifically target proteins transcribed from expression of reporter genes of interest. The purpose of this study was to develop a radioprobe that targets one of the most widely used re- porter genes, the bacterial lacZ gene. We synthesised and purified radioiodine-labelled phenylethyl-β-D-thiogalac- topyranoside (PETG), a competitive inhibitor specific against Escherichia coli β-galactosidase. We showed that [125I]iodo-PETG specifically binds to-βgalactosidase as verified by column chromatography and polyacrylamide gel electrophoresis after incubation of radiotracer with the protein. We also showed through enzyme kinetic studies that iodo-PETG retains inhibitory action against β-galactosidase activity. COS-7 cells infected with a recombinant adenovirus expressing the lacZ gene had viral titre-dependent enhancements in [125I]iodo-PETG uptake (r2=0.897; P=0.001), which reached up to 642.5%±16.7% of control levels (P<0.00001). Moreover, the level of uptake was highly correlated to luminescent measurements of β-galactosidase activity (r2=0.878; P<0.0001). These results confirm that radio- iodine-labelled PETG specifically targets -βgalactosidase and that its uptake rates faithfully reflect levels of expression of the lacZ reporter gene. Further investigations were performed in nude mice bearing human neuroblastoma tumours transferred with the lacZ gene. Compared with control tumours, lacZ-expressing tumours were slightly better visualised on [123I]iodo-PETG images and had a modest increase in tumour to muscle count ratio (2.6±0.2 vs 1.9±0.1, P<0.05). The present results provide proof-of-principle for the potential of radiolabelled inhibitors as promising radiotracers to monitor lacZ gene expression levels. Future modifica- tions to improve cell permeability should enhance in vivo contrast levels and may allow the use of radiola- belled β-galactosidase inhibitors for non-invasive monitoring of lacZ gene expression. [ABSTRACT FROM AUTHOR]

Angiostatin (AS) is a potent antiangiogenic agent which inhibits tumor growth through specific action on proliferating endothelial cells. Imaging of radiolabeled AS would enhance our knowledge on the pharmacokinetics of AS and might provide useful information relating to tumor neovasculature. We therefore investigated the potential of radiolabeled AS as a novel tumor imaging agent. Human angiostatin was radioiodine labeled using the lactoperoxidase method. Competition binding studies showed a dose-dependent inhibition of [sup 125]I-AS binding to endothelial cells by excess unlabeled AS, and a displacement curve demonstrated that specific binding was dose dependent and saturable, with a K[sub d] value of 169 nM. Gel analysis showed that [sup 125]I-AS remained stable in serum for up to 24 h without significant degradation. Intravenously injected [sup 125]I-AS in rats was cleared from the blood in an exponential fashion. Biodistribution data from human colon cancer-bearing Balb/C nude mice showed high uptake in the kidneys, stomach, liver, and lungs. Tumor uptake was 3.2±0.7, 2.6±0.2, and 1.7±0.2%ID/g at 2, 4, and 9 h after injection, respectively. Tumor to muscle count ratio increased from 3.1±0.5 at 2 h to 4.4±0.5 at 9 h. Serial scintigraphy from 1 to 5 h after [sup 123]I-AS injection demonstrated high uptake in the kidneys and bladder, consistent with renal excretion. There was clear demarcation of tumor by 1 h, with gradual increase in contrast over time (4-h tumor to contralateral thigh ratio =4.7±1.1). Thus, radioiodine-labeled angiostatin binds specifically to endothelial cells and has potential as a novel tumor imaging agent. [ABSTRACT FROM AUTHOR]