Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes

Purpose Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Procedures Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters. Results The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide. Conclusions Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions

Coronary CT Angiography: Evaluation of Stenosis and Occlusion

Once an atherosclerotic plaque has been identified and properly characterized by means of coronary CT angiography (CTA), the next step is to define the extent of atherosclerotic involvement, i.e., significant reduction of the lumen by stenosis or complete occlusion of the vessel. A reduction in the caliber of the vessel lumen is associated with a reduction in blood flow and may have significant hemodynamic consequences; however, an important and clearly evident parietal atherosclerotic plaque may be present without significantly reducing lumen caliber. Thus, an exact definition of the extent of lumen reduction by means of coronary CTA is very important from a clinical point of view. In most cases, this diagnostic procedure is employed in not highly symptomatic patients (in patients in whom there is strong clinical suspicion of coronary disease, catheter angiography is directly performed); then, depending on the results of the clinical examination, a decision is made as to whether a more invasive approach (catheter angiographsy) is required. This decision depends at least in part on the significance of the vessel stenosis. Both the aim and the key role of coronary CTA are to differentiate patients with normal coronary vessels from those with limited atherosclerotic involvement without evidence of stenosis (who may benefit from supportive drug therapy) and from those with significant stenosis. In this latter group, catheter coronary angiography may confirm the significance of the disease and define the therapeutic approach. The direct evidence of arterial stenosis provided by coronary CTA yields additional information. For example, a stenosis > 70% causes a significant hemodynamic reduction of vascular flow. Completely asymptomatic patients, with negative treadmill tests, may present with important and significant stenosis of one or more coronary arteries but with an overall reduction in flow that is less than the 70% threshold. In clinical practice, a stenosis is considered significant when the vessel caliber is reduced by > 50%. Thus, the goal is to interpret coronary CTA images such that the level of stenotic vascular involvement is precisely determined

Coronary ct angiography in heavily calcified coronary arteries: Improvement of coronary lumen visualization and coronary stenosis assessment with image postprocessing methods

To compare the diagnostic value of coronary CT angiography (CCTA) with use of 2 image postprocessing methods (CCTA_S) and (CCTA_OS) and original data (CCTA_O) for the assessment of heavily calcified plaques. Fifty patients (41 men, 9 women; mean age 61.9 years ± 9.1) with suspected coronary artery disease who underwent CCTA and invasive coronary angiography (ICA) examinations were included in the study. Image data were postprocessed with “sharpen” and smooth reconstruction algorithms in comparison with the original data without undergoing any image postprocessing to determine the effects on suppressing blooming artifacts due to heavy calcification in the coronary arteries. Minimal lumen diameter and degree of stenosis were measured and compared between CCTA_S, CCTA_OS, and CCTA_O with ICA as the reference method. The area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC) was also compared among these 3 CCTA techniques. On a per-vessel assessment, the sensitivity, specificity, positive predictive value and negative predictive value, and 95% confidence interval (CI) were 100% (95% CI: 89%, 100%), 33% (95% CI: 22%, 45%), 41% (95% CI: 30%, 53%), 100% (95% CI: 85%, 100%) for CCTA_O, 94% (95% CI: 79%, 99%), 66% (95% CI: 54%, 77%), 57% (95% CI: 43%, 70%), and 95% (95% CI: 85%, 99%) for CCTA_S, 94% (95% CI: 79%, 99%), 44% (95% CI: 32%, 57%), 44% (95% CI: 32%, 57%), and 97% (95% CI: 79%, 99%) for CCTA_OS, respectively. The AUC by ROC curve analysis for CCTA_S showed significant improvement for detection of >50% coronary stenosis in left anterior descending coronary artery compared to that of CCTA_OS and CCTA_O methods (P  0.05).CCTA with “sharpen” reconstruction reduces blooming artifacts from heavy calcification, thus, leading to significant improvement of specificity and positive predictive value of CCTA in patients with heavily calcified plaques. However, specificity is still moderate and additional functional imaging may be needed