Synthesis,Characterization, and Biological Evaluation of 99mTc(CO)3‐Labeled Peptides for Potential Use as Tumor Targeted Radiopharmaceuticals

During the past decade, several peptides containing Arg‐Gly‐Asp sequence have been conjugated with different chelating agents for labeling with various radionuclides for the diagnosis of tumor development. In this study, we report the synthesis of two tetrapeptides (Asp‐Gly‐Arg‐His and Asp‐Gly‐Arg‐Cys) and one hexapeptide [Asp‐Gly‐Arg‐D‐Tyr‐Lys‐His] by changing the amino acid sequence of the Arg‐Gly‐Asp motif. Peptide synthesis was initiated from aspartic acid. Aspartic acid placed at C‐terminal end of the peptide chain can be conjugated with different drug molecules facilitating their transport to the site of action. The peptides were synthesized in excellent yield and labeled using freshly prepared [^99mTc(CO)₃(H₂O)₃]⁺ intermediate. A complexation yield of over 97% was achieved under mild conditions even at low ligand concentrations of 10^?2 m . Radiolabeled peptides were characterized by HPLC and were found to be substantially stable in saline, in His solution as well as in rat serum and tissue (kidney, liver) homogenates. Internalization studies using Ehrlich ascites carcinoma cell line showed rapid and significant internalization (30–35% at 30 min of incubation attaining maximum value of about 40–60% after 2–4 h incubation). A good percentage of quick internalization was also observed in α_vβ₃‐receptor‐positive B16F10 mouse melanoma cell line (14–16% after 30 min of incubation and 25–30% after 2–4 h incubation). Imaging and biodistribution studies were performed in Swiss albino mice bearing Ehrlich ascites tumor in right thigh. Radiolabeled peptides exhibited fast blood clearance and rapid elimination through the urinary systems. ^99mTc(CO)₃‐tetra‐Pep2 exhibited remarkable localization at tumor site (1.15%, 1.17%, and 1.37% ID/g at 2, 4, and 6 h p.i., respectively) which could be due to slow clearance of the radiolabeled peptide from blood in comparison with the other two radiolabeled peptides. However, ^99mTc(CO)₃‐hexa‐Pep exhibited the highest tumor to muscle and tumor to blood ratios among the three. The preliminary results with these amino acid–based peptides are encouraging enough to carry out further experiments for targeting tumor.     

Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions

Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects’ ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT–RR and a trivariate \({\text{QT}}{-}{\text{RR}}{-}{\text{RESP}}\,{\text{or}}\,{\text{QT}}{-}{\text{RR}}{-}{\text{EDR}}\) model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects’ data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT–RR–RESP and QT–RR–EDR) gave significantly better fit value (p < 0.05) than that of found from the QT–RR model. EDR showed statistically similar (p > 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established the importance of using respiration and the validity of using EDR as a surrogate of respiration in the absence of respiration signal recording in linear parametric modeling of ventricular repolarization variability in healthy subjects.     

Burden of ocular morbidities and color blindness among school-attending children in a foothill town of Uttarakhand State

Purpose:To estimate prevalence of common ocular morbidities including color blindness among school-attending children of an urban foothill town of Uttarakhand State in Northern India.Methods:A cross-sectional study was conducted among school-going children of age group 6–16 years of standard I–XII. Schools were selected using population proportionate to the size sampling technique. Detailed ocular examination including color vision and unaided or aided visual acuity for various ocular morbidities was done. Data was entered into MS excel with statistical analysis using SPSS version 23 with significant P value <0.05.Results:In total, 13,492 students (mean age 10.9 ± 2.7 years) with almost equal male to female ratio were screened. Overall prevalence of ocular morbidity was 23.2%, with refractive error (18.5%) on top, followed by color blindness (2.2%). The later was observed more among males (3.0%) as compared to females (1.4%) with significantly higher odds, OR = 2.3 (1.7–2.9) (P < 0.001).Conclusion:Refractive error has been the most common ocular morbidity, followed by color blindness. Earliest detection can prevent permanent disability and disappointment among youngsters when rejected from entering certain professions due to color vision defect.