Preparation of DOTA-TATE and DOTA-NOC freeze-dried kits for formulation of patient doses of 177Lu-labeled agents and their comparison for peptide receptor radionuclide therapy application

The objective of the present work is to prepare freeze-dried DOTA-TATE and DOTA-NOC kits for the easy and convenient preparation of patient doses of ¹⁷⁷Lu-DOTA-TATE and ¹⁷⁷Lu-DOTA-NOC, respectively at the hospital radiopharmacy and to compare the radio-peptides with respect to their radiochemical and biological behaviors. Freeze-dried kits of DOTA-TATE and DOTA-NOC, comprising a lyophilized mixture of 200 μg of DOTA-peptide, 80 mg of gentisic acid and 13.9 mg of ammonium acetate were prepared. Therapeutic doses of ¹⁷⁷Lu-labeled peptides (up to 200 mCi, 7.4 GBq) were prepared using these kits and ¹⁷⁷Lu, produced in-house, with >99 % radiochemical purity and high stability following an easy and convenient protocol. Comparative pharmacokinetic behavior of the radio-peptides was studied by carrying out biodistribution studies in normal Wistar rats which revealed higher retention of activity in several major organs and slower renal clearance for ¹⁷⁷Lu-DOTA-NOC compared to that of ¹⁷⁷Lu-DOTA-TATE. Preliminary pharmacokinetic studies, carried out in limited number of patients suffering from cancers of neuroendocrine origins, showed lower accumulation of activity in vital organs and faster renal clearance of ¹⁷⁷Lu-DOTA-TATE compared to that of ¹⁷⁷Lu-DOTA-NOC.     

Synthesis and evaluation of a phenylbenzothiazole-based 99mTc(CO)3-radiotracer for possible application in imaging of β-amyloid plaques in Alzheimer’s disease

The 2-phenyl benzothiazole pharmacophore is known to have high affinity for amyloid beta (Aβ) and is therefore derivatized, to [N-(4′-benzothiazol-pyridin-2-yl-methyl-amino)-acetic acid (BTPAA)] for radiolabeling with [^99mTc(CO)₃(H₂O)₃]⁺ precursor. The radiotracer, ^99mTc(CO)₃–BTPAA is evaluated in vitro and in vivo to determine its binding with the Aβ and ability to cross the blood brain barrier. The radiotracer prepared in >95 % radiochemical yield, showed ~25 % inhibition in presence of thioflavin-T, indicating its specificity towards aggregated Aβ protein. The radiotracer also showed brain uptake of 0.25 ± 0.04 % injected dose/g at 2 min post injection, indicating its ability to cross the blood brain barrier.     

Synthesis of Pyrazole Derivatives Possessing Anticancer Activity: Current Status

Pyrazole is a versatile lead compound to design potent bioactive molecules for drug discovery and development, particularly in cancer therapy. The aim of this review is to present the most recent deeds in the field of synthetic route made for functionalized pyrazole derivatives active against cell proliferation disease. The review article covers the synthesis of 1H-pyrazole, synthesis of N-substituted pyrazoles, synthesis of pyrazolopyrazoles, and synthesis of pyrazoles fused with a naturally occurring moiety. Some of these reported compounds have passed the preclinical or initial-phase clinical trials for their anticancer activity.     

Catalytic activity of TiO2 nanoparticles in the synthesis of some 2,3-disubstituted dihydroquinazolin-4（1H）-ones

Green chemistry is playing an important role for synthesizing organic compounds, due to its eco-friendly nature and low cost. In green chemistry, metal nanoparticles exhibited some useful physical and chemical properties （catalytic activity）. Due to its diverse properties, nanoparticles can be utilized as a catalyst in various organic reactions. Recent research has been directed towards the utilization of eco- friendly and bio-friendly plant materials in nanoparticles synthesis. In our present work, TiO2 nanoparticles （TiO2 NPs） were synthesized using Annona squamosa peel extract and their catalytic applications were studied on the 2,3-disubstituted dihydroquinazolin-4（l1H）-one synthesis. Synthesized compounds were confirmed using FT-IR.1H NMR, 13C NMR and GC-MS analyses.     

Review: Raw Natural Fiber–Based Polymer Composites

The effective utilization of raw natural fibers as indispensable component in polymers for developing novel low-cost eco-friendly composites with properties such as acceptable specific strength, low density, high toughness, good thermal properties, and biodegradability is one of the most rapidly emerging fields of research in polymer engineering and science. In fact, raw natural fiber–reinforced composites are the subject of numerous scientific and research projects, as well as many commercial programs. Keeping in mind the immense advantages of raw natural fibers, in the present article we concisely review raw natural fiber/polymer matrix composites with particular focus on their mechanical properties.     

Exclusive Detection of Sub‐Nanomolar Levels of Palladium(II) in Water: An Excellent Probe for Multiple Applications

A new colorimetric probe has been developed for the detection and estimation of Pd^II at sub‐nanomolar concentrations. The probe consisted of rhodamine (signaling unit), which was linked with a bis‐picolyl moiety (binding site) through a phenyl ring. Pd^II induced opening of the spirolactam ring of the probe with the generation of a prominent pink color. The excellent selectivity of the probe towards Pd^II over Pd⁰ or Rh^II ensured its potential utility for the detection of residual palladium contamination in pharmaceutical drugs and in Pd‐catalyzed reactions. The probe showed a “turn‐on” (bright yellow) fluorescence upon the addition of Pd^II, which made it suitable for the detection of Pd contaminants in mammalian cells.     

Differential electrochemical behaviour of phytofabricated and chemically synthesized silver nanoparticles towards hydrogen peroxide sensing**

Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials for biomedical applications. However, the impact of its synthesis by chemical and plant-mediated routes on its differential electrochemical behaviour has not been examined till date. Here, we report for the first time the differential study of the electrochemical behaviour of the AgNPs synthesized by different routes. First, the AgNPs were obtained by different routes (chemical and phytofabrication) and extensively characterized to compare their physical properties. Thereafter, a comparison of electron transfer kinetics between chemically synthesized (Ag−C) and phyto-fabricated (Ag-Phy) nanoparticles (NPs) has been studied by electrochemical techniques such as potentiodynamic cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). To further investigate the electrocatalytic properties of both types of AgNPs, we have used the peroxide moieties (H₂O₂), and the Ag−C NPs-based sensor probe has been reported to have four times better sensitivity than the Ag−Phy NPs-based sensor. The AgNPs modified sensor probes have also been tested in real-world environments to explore the consistency of their performance in complex matrices by using clinical urine samples, where we found comparable sensitivity to the standard conditions.     

T2 relaxation time measurements in osteoarthritis

Quantification of changes in T(2) relaxation time, in human cartilage, with progression of osteoarthritis (OA), and evaluation of qualitative correlations with clinical evaluation, histology and polarized light microscopy (PLM). Cartilage-bone plugs were harvested from fresh cadaveric knees (n = 10) and specimens after surgical knee replacement (n = 2) at 12 locations, including lateral and medial sides of tibia, femora and patella. Magnetic resonance imaging was performed at 1.5 Tesla using a.2D spin echo sequence. Histological slices were assessed for OA severity through a grading scale based on combined histological and PLM results. T(2) values in clinically moderate OA were generally higher than in severe OA and normal cartilage. Significant association was established between normal and early OA subjects and T(2) variation, in the medial compartment of the knee (p < 0.05) but especially in the medial tibial cartilage (p < 0.00005). As expected, medial and lateral tibio-femoral compartments underwent more severe degeneration. Additionally, there were intracompartmental variation of the relaxation times and histological patterns, which demonstrate the underlying focal involvement of OA in the knee. Furthermore, T(2) values reflected OA pathogenesis with a positive correlation with histology grading scale. Finally, increased T(2) is correlated to histological degeneration of cartilage and may be a good marker for early OA in tibial articular cartilage.     

A study of the relationship between molecular biomarkers of joint degeneration and the magnetic resonance-measured characteristics of cartilage in 16 symptomatic knees

We used quantitative magnetic resonance (MR) imaging to determine if relationships exist between proposed molecular biomarkers for degenerative joint disease (DJD) and structural characteristics of articular cartilage. Subjects were eight male and eight female volunteers diagnosed with osteoarthritis. Magnetic resonance images of the symptomatic knee were taken and blood samples were drawn. Concentrations of serum cartilage oligomeric matrix protein (COMP) and cleaved collagen neoepitope were compared to cartilage volume and cartilage T2, respectively, in four compartments of the tibiofemoral joint. A significant, negative correlation was found between serum COMP and medial tibia volume in the male subject group (rho=-.738, P=.037). A significant, positive correlation (rho=.881, P=.0039) was found between serum COMP and lateral femur volume in the female subject group. In both groups, positive correlations were found between serum C2C and cartilage T2, which were significant in two compartments of the male group (rho=.714, P=.047; rho=.738, P=.037) and similarly strong, but not statistically significant (rho=.750, P=.052), in one compartment of the female group. We identify strong and biologically relevant correlations between two proposed molecular biomarkers for DJD and MR measures of symptomatic knees of a small number of arthritic patients. Our findings support the hypothesis that cartilage molecular biomarkers reflect the molecular processes of cartilage degeneration and loss.     

Electronic states and pseudo Jahn-Teller distortion of heavy metal-monobenzene complexes: M(C6H6) (M = Y, La, and Lu)

Monobenzene complexes of yttrium (Y), lanthanum (La), and lutetium (Lu), M(C(6)H(6)) (M = Y, La, and Lu), were prepared in a laser-vaporization supersonic molecular beam source and studied by pulsed-field ionization zero electron kinetic energy (ZEKE) spectroscopy and ab initio calculations. The calculations included the second-order perturbation, the coupled cluster with single, double, and perturbative triple excitation, and the complete active space self-consistent field methods. Adiabatic ionization energies and metal-benzene stretching frequencies of these complexes were measured for the first time from the ZEKE spectra. Electronic states of the neutral and ion complexes and benzene ring deformation were determined by combining the spectroscopic measurements with the theoretical calculations. The ionization energies of M(C(6)H(6)) are 5.0908 (6), 4.5651 (6), and 5.5106 (6) eV, and the metal-ligand stretching frequencies of [M(C(6)H(6))](+) are 328, 295, and 270 cm(-1) for M = Y, La, and Lu, respectively. The ground states of M(C(6)H(6)) and [M(C(6)H(6))](+) are (2)A(1) and (1)A(1), respectively, and their molecular structures are in C(2v) point group with a bent benzene ring. The deformation of the benzene ring upon metal coordination is caused by the pseudo Jahn-Teller interaction of (1(2)E(2)+1(2)A(1)+2(2)E(2)) e(2) at C(6v) symmetry. In addition, the study shows that spectroscopic behaviors of Y(C(6)H(6)) and La(C(6)H(6)) are similar to each other, but different from that of Lu(C(6)H(6)).