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Featured Articles
Scientific literature: molecular imaging
The number of peer-reviewed papers covering the field of molecular imaging is huge, to such an extent that it is frequently difficult for healthcare professionals to keep up with the literature. As a special service to our readers, International Hospital presents a few key literature abstracts from the clinical and scientific literature chosen by our editorial board as being particularly worthy of attention.
Non-invasive imaging of PI3K/Akt/mTOR signalling in cancer
Snehal MG, Pritha R. Am J Nucl Med Mol Imaging 2012; 2(4): 418-431.
Platinum based drugs are widely used to treat various types of cancers by inducing DNA damage mediated cytotoxicity. However, acquirement of chemoresistance towards platinum based drugs is a common phenomenon and a major hurdle in combating the relapse of the disease. Oncogenesis and chemoresistance are multifactorial maladies which often involve deregulation of one of the prime cell survival pathways, the PI3K/Akt/mTOR signalling cascade. The genetic alterations related to this pathway are often responsible for initiation and/or maintenance of carcinogenesis. Molecular components of this pathway are long being recognized as major targets for therapeutic intervention and have now also emerged as potential tools for diagnosis of cancer. To develop novel therapeutics against the key molecules of PI3K pathway, stringent validation is required using both in-vitro and in-vivo models. Repetitive and non-invasive molecular imaging techniques, a relatively recent field in biomedical imaging, hold great promises for monitoring such diagnosis and therapy. This review introduces the PI3K/Akt/mTOR pathway and its role in acquirement of chemoresistance in various cancers. Further is described how non-invasive molecular imaging approaches are sought to use this PI3K signalling axis for the therapeutics and diagnosis. A theranostic approach using various imaging modalities should be the future of PI3K signalling based drug development venture.
Quantitative longitudinal imaging of vascular inflammation and treatment by Ezetimibe in apoE mice by FMT using new optical imaging biomarkers of cathepsin activity and integrin
Shu-An Lin et al. Inter Jour Mol Imaging. 2012 Sept. Article ID 189254.
Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of integrin. In this study fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities was employed using cathepsin sensing (ProSense, CatB FAST) and integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE−/− mice () versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7 mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated () versus untreated apoE−/− mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients.
18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors
Yarasheski KE et al. Jour. of Inflammation 2012 June; 9: 26.
Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular 18Fluorodeoxyglucose (18FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. The study hypothesized that 18FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk and studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m2, median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m2, no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). 18FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. 18FDG uptake into both carotid arteries and the aorta was compared between the two groups. Right and left carotid 18FDG uptake was greater (P < 0.03) in the HIV group (1.77
Proadrenomedullin biomarker improves risk stratification and site of care decision in pneumonia patients
Initial severity assessment of emergency department patients with lower respiratory tract infections (LRTI) remains a clinical challenge. IHE spoke to Dr Philipp Schuetz, associate professor of internal medicine of the Medical University Clinic in Aarau, Switzerland, about his experience with ProADM, a new biomarker that has great potential to improve the current triage practice and thus site of care decisions.
Q. Is the risk assessment of patients who suffer from lower respiratory tract infection (LRTI) still a clinical need in hospitals?
Yes, LRTI is a serious condition associated with a significant rate of morbidity and long-term mortality. Additionally, LRTI has a major impact on the use of resources and healthcare expenditure. Although most patients are treated on an outpatient basis, the costs for hospitalized pneumonia patients can be 25 times higher [1]. Therefore, whether or not to hospitalize a patient is clinically of outmost importance and a very costly decision. Severity scores such as Pneumonia Severity Index (PSI) and/or the CURB65 were developed to aid the site of care decision and safely assess the risk of pneumonia patients. However, these scores have significant shortcomings which limit their applicability in routine care. First of all, they focus on mortality only, rather than on other complications, Secondly, they are static and do not include changes of the condition over time. Finally, they perform sub-optimally which should be improved to be able to make safe decisions for individual patients. Thus, there is still room to improve the current risk assessment tools and blood biomarkers like Proadrenomedullin (ProADM) which seems to show great potential in filling this gap [2-5].
Q. What is ProADM? How does it improve risk assessment in LRTI patients?
ProADM (mid-regional proAdrenomedullin) is a stable surrogate marker for Adrenomedullin (ADM). ADM belongs to the family of Calcitonin related peptides, similar to Procalcitonin (PCT). ADM is the most potent vasodilator and is activated in different stages of severe illness, such as sepsis and systemic infections. Unlike PCT, ADM is not specific to infections, but increases in different conditions that correlate with severity and adverse outcome across different medical diseases. Therefore, ProADM is not a diagnostic marker for sepsis, but has prognostic abilities. Importantly, proADM is also dynamic over time and the levels decrease when a patient improves; it also correlates with the risk of adverse events.
In several studies, ProADM showed a high correlation with the severity of LRTI; it was better than other commonly used parameters (WBC, PCT and CRP) and as powerful as PSI and CURB-65. Interestingly, when ProADM was used in addition to clinical risk scores, the accuracy of PSI and CURB-65 for risk prediction was improved for both short-term and long-term mortality.
Q. What is the benefit of adding ProADM to clinical risk assessment?
ProADM allows physicians to objectively estimate a patient
Scientific literature review: MR
The number of peer-reviewed papers covering the field of magnetic resonance (MR) is huge, to such an extent that it is frequently difficult for healthcare professionals to keep up with the literature. As a special service to our readers, International Hospital presents a few key literature abstracts from the clinical and scientific literature chosen by our editorial board as being particularly worthy of attention.
Clinical MRI of acute ischemic stroke
Gilberto Gonz
Private hospitals in China and India: medical equipment demand to soar
Depending on who is speaking, the rise of China and India is seen as an opportunity, a threat or a mix of both. Measured by purchasing power, the World Bank lists the two Asian giants as the world
