Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies

Performance of Higher National Diploma of Building Technology Graduates in the Construction Industry: A Tracer Study in Kumasi Metropolis, Ghana

Building Technology graduates from Ghanaian Polytechnics seek employment in the construction industry, yet little information is known as to whether their tertiary education is really related to and meeting the actual needs of their prospective employers in the construction industry. The tracer study was conducted to ascertain the performance of Higher National Diploma (HND) Building Technology graduates and the extent to which their academic training meets the employers’ needs in the construction industry. In order to obtain a good assessment of the skills (technical and non-technical) and competencies of Polytechnic HND building Technology graduates, purposive sampling technique was used. Construction firms with Ministry of Water Resources, Works and Housing classification of D3K3 and above who have been in operation for a minimum of one year and have employed Polytechnic HND Building Technology graduates were identified. Out of the firms identified, thirty-five (35) were selected using simple random sampling technique. A Structured questionnaire was designed and distributed to site engineers, site supervisors, quantity surveyors, operation managers and project managers in the selected construction firms. Descriptive statistic was used to analyse the data using. The study revealed that Polytechnic HND graduates in the construction industry were performing creditably since the index of performance of site supervisors, quantity surveyors and site managers were generally above average. Apart from the academic competence, graduates possessed non-academic attributes which the employers emphasized as criteria for graduates’ employability and performance in the construction industry. These attributes included verbal communication, teamwork, time management, commitment and interpersonal skills. Keywords: Building Technology, Graduates, Polytechnic, Construction Industry, Performanc

Protein and energy requirements for indigenous guinea keets (Numida meleagris) in southern Ghana

One thousand two hundred healthy unsexed unsexed keets were used in an 8-week feeding trial that aimed at determining the protein and energy requirements during the starter phase of local guinea fowls reared in coastal savanna part of Ghana. The keets were randomly allocated in a 3 X 2 factorial design to six dietary treatments (three crude protein levels and two energy levels) in a deep litter system. Each treatment had 200 keets and was replicated four times with 50 keets per replicate. The six dietary treatments were designated as follows: T1 (23% CP and 11.5 MJ ME/kg), T2 (24% CP and 11.5 MJ ME/kg), T3 (25% CP and 11.5 MJ ME/kg), T4 (23% CP and 12.5 MJ ME/kg), T5 (24% CP and 12.5 MJ ME/kg), and T6 (25% CP and 12.5 MJ ME/kg). A known daily quantity of feed was given each replicate early in the morning while water was provided ad libitum. The same diets were fed for the entire duration of the study. Feed intake, weight gain, feed conversion ratio, economy of gain and mortality were determined and use as indices of evaluation. The feed intake per keet per day increased with the lower energy level diets (T1, T2 and T3) (P < 0.05). Dietary treatments T5 and T6 had the highest (P < 0.05) daily weight gains of 8.61 and 8.38 g/day respectively. The feed conversion ratios of the keets were 4.18, 4.20, 4.13, 4.32, 3.46 and 3.60 for T1, T2, T3, T4, T5 and T6, respectively. T5 diet had the least (P < 0.05) feed costs per kg gain ($/kg gain) value of 1.63. The study indicated that protein and energy required by guinea keets during the first 8 weeks of growth could be put at 24 percent CP and 12.5 MJ ME/kg, respectively

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

Women as construction professionals: modern day challenges

The ratio of men to women in the construction industry is one that has often attracted great concern for all stakeholders. Although the UK construction sector has enjoyed a significant rise in the number of women, there is undoubtedly more room for improvement. Numerous schemes have been initiated by government and other professional bodies to encourage more women to join the industry. On the surface, many issues such as lack of workplace flexibility and looming discrimination prevent many more women from joining. Using the glass ceiling and the leaky pipeline theories, an in-depth exploration of experiences of female construction professionals is undertaken in this research. A total of six semi-structured interviews were carried out. Although the respondents acknowledged the industry had improved significantly, they nevertheless expressed concerns on many issues that they believed needed to be addressed. It was identified that many women struggle to re-enter the industry after embarking on maternity leave. Furthermore, the respondents believed that some workplace progressions were only due to senior managers’ attempt to demonstrate a level of inclusivity rather than due to merit. Finally, it was revealed that sexism is still rife in the industry and many women are left in very uncomfortable environments with fear of voicing out this horror. This research merely offers a peek at the ordeals that some women have to endure when working in the construction industry. Hopefully by addressing such issues, more women will be encouraged to take up professions in the sector

A phase I study of the nitroimidazole hypoxia marker SR4554 using 19F magnetic resonance spectroscopy

SR4554 is a fluorine-containing 2-nitroimidazole, designed as a hypoxia marker detectable with 19F magnetic resonance spectroscopy (MRS). In an initial phase I study of SR4554, nausea/vomiting was found to be dose-limiting, and 1400 mg m−2 was established as MTD. Preliminary MRS studies demonstrated some evidence of 19F retention in tumour. In this study we investigated higher doses of SR4554 and intratumoral localisation of the 19F MRS signal. Patients had tumours 3 cm in diameter and 4 cm deep. Measurements were performed using 1H/19F surface coils and localised 19F MRS acquisition. SR4554 was administered at 1400 mg m−2, with subsequent increase to 2600 mg m−2 using prophylactic metoclopramide. Spectra were obtained immediately post infusion (MRS no. 1), at 16 h (MRS no. 2) and 20 h (MRS no. 3), based on the SR4554 half-life of 3.5 h determined from a previous study. 19Fluorine retention index (%) was defined as (MRS no. 2/MRS no. 1)*100. A total of 26 patients enrolled at: 1400 (n=16), 1800 (n=1), 2200 (n=1) and 2600 mg m−2 (n=8). SR4554 was well tolerated and toxicities were all grade 1; mean plasma elimination half-life was 3.7±0.9 h. SR4554 signal was seen on both unlocalised and localised MRS no. 1 in all patients. Localised 19F signals were detected at MRS no. 2 in 5 out of 9 patients and 4 out of 5 patients at MRS no. 3. The mean retention index in tumour was 13.6 (range 0.6-43.7) compared with 4.1 (range 0.6-7.3) for plasma samples taken at the same times (P=0.001) suggesting 19F retention in tumour and, therefore, the presence of hypoxia. We have demonstrated the feasibility of using 19F MRS with SR4554 as a potential method of detecting hypoxia. Certain patients showed evidence of 19F retention in tumour, supporting further development of this technique for detection of tumour hypoxia

Detecting Schistosoma mansoni infections among pre-school-aged children in southern Ghana: a diagnostic comparison of urine-CCA, real-time PCR and Kato-Katz assays

Background In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. Methods In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. Results Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4–96.4), 87.9% (95% CI 76.7–95), and 81.2% (95% CI 69.9–89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5–64.5), 8% (95% CI 2.2–19.2) and 16.7% (95% CI 8.3–28.5), while by Kato-Katz was 55.6% (95% CI 42.5–68.1), 8.6% (95% CI 2.9–19) and 11.6% (95% CI 5.1–21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3–4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7–92.1) and 12.9% (95% CI = 6.6–22) respectively. Conclusions We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration

The Curative and Prophylactic Effects of Xylopic Acid on Plasmodium berghei

Efforts have been intensified to search for more effective antimalarial agents because of the observed failure of some artemisinin-based combination therapy (ACT) treatments of malaria in Ghana. Xylopic acid, a pure compound isolated from the fruits of the Xylopia aethiopica, was investigated to establish its attributable prophylactic, curative antimalarial, and antipyretic properties. The antimalarial properties were determined by employing xylopic acid (10–100 mg/kg) in ICR mice infected with Plasmodium berghei. Xylopic acid exerted significant (P<0.05) effects on P. berghei infection similar to artemether/lumefantrine, the standard drug. Furthermore, it significantly (P<0.05) reduced the lipopolysaccharide- (LPS-) induced fever in Sprague-Dawley rats similar to prednisolone. Xylopic acid therefore possesses prophylactic and curative antimalarial as well as antipyretic properties which makes it an ideal antimalarial agent