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ntroduction: Multiple sclerosis (MS) is characterised by demyelination, but it is known from pathology studies that inflammation, evidenced by infiltrating immune cells and activated microglia in normal appearing white matter (NAWM), is also present at different disease stages. The effects of inflammation on MS progression are not yet understood; positron emission tomography (PET) offers the opportunity to monitor these effects and thus aid patient stratification and guide therapy selection, adding to the information already available from MRI techniques. The 18 kDa translocator protein (TSPO) is upregulated in activated microglia, which are present in inflammatory lesions and NAWM in MS. [11C]-(R)-PK11195 is a TSPO-PET ligand which is known to show localisation and extent of inflammation in many brain diseases, including MS, but suffers from a poor signal to noise ratio (SNR) and short (20 minutes) half-life. [18F]GE-180 is a novel TSPO-PET ligand which has shown improved SNR and lower non-specific binding than [11C]-(R)-PK11195 in pre-clinical models. Here, we present initial results from a phase 1 study in relapsing-remitting MS (rrMS) and healthy control subjects (HVs).Methods: HVs and rrMS subjects were assessed for binding status. One non-binder in each group was included. Subjects underwent T1 pre and post gadolinium enhanced MRI scans and T2 scans additionally. 90 minute dynamic [18F]GE-180 PET scans were performed typically within 1 month. PET and T1 pre-contrast MR images were co-registered in the software package PMOD, and the Hammers atlas was applied to acquire standardised uptake values (SUVs) for regions of interest (ROIs). Selected areas of T2 hyperintensity were defined manually to give MS lesion SUVs. A cortical composite grey matter (GM) region was chosen as reference for SUVRs. Results: No Gd-enhancing lesions were identifiable from T1 post-contrast MRIs. With [18F]GE-180, whole WM uptake (SUVRGM) was slightly higher in rrMS than HVs, while a lesion-rich periventricular (PV) area yielded SUVRs which were approximately 10% higher in rrMS than HVs. PET-defined lesions in rrMS showed an elevation of 20 - 40% compared to HVs.Conclusion: Preliminary results suggest that [18F]GE-180 is able to identify areas of inflammation in PET images which are non-Gd-enhancing in T1.Disclosure: The data presented are from a GE Healthcare sponsored phase 1 clinical trial.William Trigg, Chris Buckley, Kerstin Heurling, David Brooks and Paul Sherwin are or were employees of GE Healthcare.Sujata Sridharan receives partial funding for her PhD studies from GE Healthcare and is Supervised by Rainer Hinz who has nothing to disclose.MaryLou Lawler, Janet Crouch, Karen Gulenchyn, Shelley Amodeo and J.E. Rick Paulseth are employees of Hamilton Health Sciences where the studies were carried out.The studies were funded by GE Healthcare.

Although willingness, attitudes and beliefs surrounding solid-organ donation have been extensively investigated, much less is known about corneal donation. Despite evidence that a substantial number of families who agree to multiorgan donation also specifically refuse corneal donation, it is unclear why this occurs and what can be done to increase rates of corneal donation. We conducted a survey of 371 Australian adults regarding their views on corneal donation. Although willingness to donate corneas generally reflected a person's willingness to donate all of one's organs, unwillingness to donate corneas appeared to be due to other factors. Specifically, decisions not to donate appear to be driven by a range of concerns surrounding disfigurement. The survey also provides eye banks with reassurance about the acceptability of whole globe procurement, and recognition that research into blindness is a highly valued part of corneal donation. Finally, the survey identifies that many individuals see benefit in having their family engaged in the decision-making process, suggesting that decisions about donation are more complex than a simple appeal to the autonomy of the deceased. Funding Sources: The Ophthalmic Research Institute of Australia (ORIA), The Sydney Eye Hospital Foundation

Consent to organ and tissue donation is higher when the deceased has indicated a wish to donate. The Australian Organ Donor Register (AODR) is the national register of preferences regarding donation. The AODR has a number of limitations; it has no mechanism for requiring individuals to register their wishes, while the online format both raises concerns about the validity of the consent obtained and precludes personal discussion of fears and concerns about donation. A solution to these limitations is to utilize state-based agencies that administer driving licences. This strategy ties the donation decision to an existing task (renewal of driving licences), and provides an opportunity for a personalized intervention at the time the decision is being made.

The formation of the unique fusion gene, bcr-abl, and the resultant increase in abl tyrosine kinase activity, is seen as the major driving force in the initiation of chronic myelogenous leukaemia (CML). The deregulation of abl tyrosine kinase activity, brought about by the binding of a portion of the Scr molecule to the SH2 regulatory domain of abl, appears to play a role in promoting resistance to drug-induced apoptosis. Thus the large increase In mature myeloid cells seen in CML could be the direct result of the suppression of apoptosis by the bcr-abl fusion protein. The role and contribution of apoptosis in the progression of CML and the possible role of antisense oligonucleotides to the bcr-abl gene as therapeutic agents is discussed.