ABSTRACT
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.
ABSTRACT
BACKGROUND: Dental decay in early childhood can be prevented by a model based on shared care utilising members of primary care team such as Child and Family Health Nurses (CFHNs) in health promotion and early intervention. The aims of this study were to identify the facilitators and barriers faced by CFHNs in recruiting research participants from disadvantaged backgrounds to a birth cohort study in South Western Sydney, Australia. METHODS: Child and Family Health Nurses recruited mothers-infants dyads (n = 1036) at the first post-natal home visit as part of Healthy Smiles Healthy Kids Study, an ongoing birth cohort study in South Western Sydney. The nurses (n = 19) were purposively selected and approached for a phone based in-depth semi-structured interview to identify the challenges faced by them during the recruitment process. Interviews were audio-recorded, subsequently transcribed verbatim and analysed by thematic analysis. RESULTS: The nurses found the early phase of parenting was an overwhelming stage for parents as they are pre-occupied with more immediate issues such as settling and feeding a newborn. They highlighted some key time-points such as during pregnancy and/or around the time of infant teething may be more appropriate for recruiting families to dental research projects. However, they found it easier to secure the family's attention by offering incentives, gifts and invitations for free oral health services. The use of web-based approaches and maintaining regular contact with the participants was deemed crucial for long-term research. Cultural and linguistic barriers were seen as an obstacle in recruiting ethnic minority populations and the need for cultural insiders in the research team was deemed important to resolve the challenges associated with conducting research with diverse cultures. Finally, nurses identified the importance of inter-professional collaboration to provide easier access to recruiting research participants. CONCLUSIONS: This study highlighted the need for multiple time-points and incentives to facilitate recruitment and retention of disadvantaged communities in longitudinal research. The need for cultural insiders and inter-professional collaboration in research team are important to improve research participation.
