A review of approaches to 18F radiolabelling affinity peptides and proteins

Affinity peptide and protein‐ (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. ¹⁸F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, ¹⁸F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to ¹⁸F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site‐specific methodologies with an impetus for short, automated procedures which produce high‐yielding [¹⁸F]APPs.     

Treatment sequence network meta-analysis in Crohn’s disease: a methodological case study

Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.

Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.

Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.

Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.     

The impact of two-dimensional versus three-dimensional ultrasound exposure on maternal-fetal attachment and maternal health behavior in pregnancy.

OBJECTIVE: To explore the impact of timing and type of ultrasound, particularly three-dimensional (3D), exposure on maternal-fetal attachment and maternal health behavior during pregnancy. METHODS: Subjects were 68 women aged 18 years or older expecting their first child who presented for a routine ultrasound scan at around either 12 or 18 weeks' gestation in Nepean Hospital, Western Sydney. Women completed questionnaires assessing maternal-fetal attachment and health behavior, and were then allocated arbitrarily to either two-dimensional (2D) or 3D ultrasound examination. Repeat questionnaires were completed 1 week later. RESULTS: Maternal-fetal attachment increased after both 2D and 3D ultrasound exposure, and the effect was moderated by the timing of exposure, with women receiving their first ultrasound examination at around 12 weeks showing the greatest change. Alcohol consumption was the only behavior to show significant change following ultrasound exposure, with a reduction in the reported average number of drinks per week. There was no significant difference in the pattern of change for 2D compared with 3D ultrasound exposure, and no effect of ultrasound exposure on maternal perception of the fetus. CONCLUSIONS: Ultrasound has a positive impact on maternal-fetal attachment, particularly in the first trimester. 3D ultrasound did not offer enhanced benefits. Associations between ultrasound exposure and alcohol consumption warrant further investigation. Larger samples are needed to clarify the moderating effects of gestational age and type of ultrasound exposure.