Background: Primary right-sided colon cancer (RCC) is associated with a higher mortality than left-sided colon cancer (LCC), but the etiology of this phenomenon remains unclear. We sought to study whether cancer laterality is associated with the prevalence of clinical coronary artery disease, calcific atherosclerosis as measured by computed tomography (CT), and cardiovascular risk factors. Methods: We conducted a single center retrospective study of 546 participants who had previously been diagnosed with colon cancer between January 2005 and December 2014. The presence of coronary and aortic calcifications was assessed by CT in 486 of these patients. We examined the prevalence of clinical cardiovascular disease (CAD) (prior myocardial infarction or revascularization), comorbidities, coronary and aortic calcification in patients with RCC (n=261) and LCC (n=285). Logistic regression analysis was performed to assess the likelihood of clinical CAD and calcific atherosclerosis by cancer laterality. Results: Compared to patients with LCC, patients with RCC were more likely to have hypertension, hyperlipidemia, hypothyroidism and clinical CAD. In the patients with available CT scans, RCC was associated with higher prevalence of coronary, thoracic, and abdominal calcifications than LCC. On univariate and multivariate analyses, RCC was associated with higher likelihood of clinical CAD (adjusted risk ratio 2.15, 95% CI, 1.37-3.38, P=0.001) as well as radiological evidence of calcific atherosclerosis compared to LCC. Conclusions: we found that both clinical CAD and vascular calcifications are prevalent in patients with colon cancer, and are independently increased in patients with RCC compared to LCC.

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Transferrin (Tfn) is commonly used as a drug delivery carrier for cancer treat ment. Tfn receptor dimerization, and internalization, can be observed by Förster resonance energy transfer (FRET), which occurs when two fluorophoresdonor and acceptor -are a few nanometers apart. Donor fluorescence lifetime can be used to sense and quantify FRET occurrence. In FRET state, the donor is quenched leading to a significant reduction in its lifetime. In this study, donor and acceptor near-infrared (NIR) fluorophore-labeled Tfn were used to quantify cellular internalization in breast cancer cell line (T47D). Based on donor lifetime, quantum yield and spectral data, five NIR FRET pairs were chosen for this comparison. Performance of the different NIR FRET pairs was evaluated in vitro in multiwell plate settings and by analyzing the relationship between quenched donor fraction and acceptor to donor ratio. Additionally, we performed brightness comparison between each pairs. Several parameters, such as brightness, lifetime, R0 and FRET donor population values are used to identify the most suitable NIR FRET pair for in vivo studies in pre-clinical settings.

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Near-Infrared fluorophore pairs were comparatively studied to perform quantitative lifetime-based FRET imaging. The best pair, as defined as the brightest and leading to accurate estimation of FRET component, is suitable for pre-clinical application. OCIS codes: (170.3880) Medical and biological imaging; (170.6920) Time-resolved imaging IntroductionTargeted drug delivery has been studied for decades to improve therapeutic index of drugs, particularly cancer drugs. Transferrin (Tfn) is one of the most common molecule used as a receptor-mediated drug and gene delivery vehicle for diagnosis treatment of medical conditions [1]. Tfn can be used for deliver drugs for treatment of cancers as malignant cells express more transferrin receptor (TfR) [2]. The homo-dimerization of transferrin receptors during endocytosis provides a few nanometers distance between two transferrin molecules. At this distance, Förster resonance energy transfer (FRET) occurs. Hence, FRET imaging may be used to sense and quantify TfR-Tfn uptake into tumor cells.FRET is a phenomenon where two fluorescent molecules, a donor and an acceptor, are close to each other within 2-10 nanometers distance. During FRET state, the donor transfers the photon energy to the acceptor; the donor fluorescent intensity is reduced. The lifetime of the donor, another characteristic that can be observed, is also significantly reduced. The efficiency of FRET largely depends on the distance between donor and acceptor. Specifically, the efficiency is inversely proportional to the sixth power of the distance. The Förster distance (R0) is the distance where the efficiency is 50%. The larger R0 provides more chance of FRET phenomenon. The donor emission spectrum must overlap the acceptor excitation spectrum for a certain degree to provide sufficient energy transfer. The spectral overlap is the characteristic of the donor-acceptor pair and it affects R0 as well. Hence, FRET imaging performances are highly dependent on the fluorophore pair employed.Near-infrared (NIR) fluorophores are attractive for imaging as they are less affected by the interaction of photons with biological specimens. Most components of cells and tissue absorb the photons at visible spectrum. Proteins are the main component absorbing the light at UV to visible spectrum. Absorption of photons in vivo is primarily influenced by hemoglobin, melanin, fat and water. The absorption coefficients of these components are minimal in the NIR spectrum [3]. Furthermore, in vivo fluorescence imaging is affected by autofluoresence of endogenous fluorophores from extracellular matrix proteins. Autofluorescence mainly occurs from the UV to the visible spectrum and is relatively weak in the NIR. Because of these biological interactions, near-infrared fluorophores are the most suitable for in vitro and in vivo biological imaging applications. However, these fluorophores usually have shorter lifetime than visible fluorophores. These shorter lifetimes are challenging to resolve in time-resolved imaging as the lifetime may be cl...