The innovative 52g Mn for positron emission tomography (PET) imaging: Production cross section modeling and dosimetric evaluation.

BACKGROUND: Manganese is a paramagnetic element suitable for magnetic resonance imaging (MRI) of neuronal function. However, high concentrations of Mn2 + can be neurotoxic. 52g Mn may be a valid alternative as positron emission tomography (PET) imaging agent, to obtain information similar to that delivered by MRI but using trace levels of Mn2 + , thus reducing its toxicity. Recently, the reaction n a t $^{nat}$ V(α,x)52g Mn has been proposed as a possible alternative to the standard n a t $^{nat}$ Cr(p,x)52g Mn one, but improvements in the modeling were needed to better compare the two production routes. PURPOSE: This work focuses on the development of precise simulations and models to compare the 52g Mn production from both reactions in terms of amount of activity and radionuclidic purity (RNP), as well as in terms of dose increase (DI) due to the co-produced radioactive contaminants, versus pure 52g MnCl2 . METHODS: The nuclear code Talys has been employed to optimize the n a t $^{nat}$ V(α,x)52g Mn cross section by tuning the parameters of the microscopic level densities. Thick-target yields have been calculated from the expression of the rates as energy convolution of cross sections and stopping powers, and finally integrating the time evolution of the relevant decay chains. Dosimetric assessments of [ x x $^{xx}$ Mn]Cl2 have been accomplished with OLINDA software 2.2.0 using female and male adult phantoms and biodistribution data for 52g MnCl2 in normal mice. At the end, the yield of x x $^{xx}$ Mn radioisotopes estimated for the two production routes have been combined with the dosimetric results, to assess the DI at different times after the end of the irradiation. RESULTS: Good agreement was obtained between cross-section calculations and measurements. The comparison of the two reaction channels suggests that n a t $^{nat}$ V(α,x)52g Mn leads to higher yield and higher purity, resulting in more favorable radiation dosimetry for patients. CONCLUSIONS: Both n a t $^{nat}$ V(α,x) and n a t $^{nat}$ Cr(p,x) production routes provide clinically acceptable 52g MnCl2 for PET imaging. However, the n a t $^{nat}$ V(α,x)52g Mn reaction provides a DI systematically lower than the one obtainable with n a t $^{nat}$ Cr(p,x)52g Mn and a longer time window in which it can be used clinically (RNP ≥ 99%).

Total hip arthroplasty planning.

Preoperative planning is mandatory to achieve the restoration of a correct and personalized biomechanics of the hip.The radiographic review is the first and fundamental step in the planning. Limb or pelvis malpositioning during the review results in mislead planning.Correct templating is possible using three different methods: acetate templating on digital X-ray, digital 2D templating on digital X-ray and 3D digital templating on CT scan.Time efficiency, costs, reproducibility and accuracy must be considered when comparing different templating methods. Based on these parameters, acetate templating should not be abandoned; digital templating allows a permanent record of planning and can be electronically viewed by different members of surgical team; 3D templating is intrinsically more accurate. There is no evidence in the few recently published studies that 3D templating impacts positively on clinical outcomes except in difficult cases.The transverse acetabular ligament (TAL) is a reliable intraoperative soft tissue reference to set cup position.Spine-hip relations in osteoarthritic patients undergoing hip joint replacement must be considered. Cite this article: EFORT Open Rev 2019;4:626-632. DOI: 10.1302/2058-5241.4.180075.

Plasma clusterin as a candidate pre-diagnosis marker of colorectal cancer risk in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition: a pilot study.

BACKGROUND: Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis. METHODS: After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case-control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed. RESULTS: Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann-Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein's unit increase, but only in men. CONCLUSIONS: The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.

Effects of cigarette smoking on the human urinary proteome.

In this pilot study we used a proteomic approach to compare the urinary protein patterns of healthy smokers and non-smokers. Proteins were resolved by two-dimensional gel electrophoresis and identified by mass spectrometry. The relative abundance of three inflammatory proteins (S100A8, inter-alpha-trypsin inhibitor heavy chain 4, CD59) and that of two isoforms of pancreatic alpha amylase was significantly higher in smokers. Zinc-alpha-2-glycoprotein was the only protein down-regulated in smokers. Its abundance was significantly correlated with urinary glucocorticoids. Most of the proteins identified may be non-specific biomarkers of tobacco effects, since they are involved in inflammatory responses associated with several diseases. Of greater interest are the changes in abundance of pancreatic alpha amylase and zinc-alpha-2-glycoprotein, which after proper validation, might be candidate biomarkers of diseases resulting from exposure to tobacco smoke. The data also show for the first time that smoking can affect the expression profile of urinary proteins.

Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study.

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.

4-Aminobiphenyl-hemoglobin adducts and risk of smoking-related disease in never smokers and former smokers in the European Prospective Investigation into Cancer and Nutrition prospective study.

The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, involving 190 controls and 149 cases (incident cancer of the lung, bladder, pharynx, larynx, oral cavity, leukemias, and chronic obstructive pulmonary disease or emphysema deaths). All individuals were never smokers or ex smokers for >10 years. 4-ABP-Hb adducts were analyzed in peripheral blood collected before the onset of the disease (median, 7 years). Overall, 4-ABP-Hb adducts were higher, although not statistically significantly so, in cases (as a whole) than controls. In the control population, high fruit and vegetable consumption significantly lowered the frequency of detectable adducts (Fisher's exact test, P = 0.025). Restricting the analysis to women, 4-ABP-Hb adducts were higher in cases than controls (Mann-Whitney P = 0.036) and the odds ratio (OR) for the presence/absence of adducts was 2.42 [95% confidence interval (95% CI), 1.18-4.98]. Moreover, the association of adducts with the individual cancer types was stronger in women than in the whole study population, although statistically significant only for leukemias (OR, 2.77; 95% CI, 1.06-7.20). The results provide some evidence that women may be more susceptible to environmental tobacco smoke, as suggested by their higher adduct levels. The most important finding of this prospective study is that, at least in women, 4-ABP-Hb adducts may help identify subjects at high risk of cancers related to environmental tobacco smoke exposure.