Detailed Chemistry Studies of 225Actinium Labeled Radiopharmaceuticals

2021 ◽  
Vol 14 ◽  
Author(s):  
Kurtulus Eryilmaz ◽  
Benan Kilbas
Keyword(s):  
Water Solution ◽  
Radiochemical Yield ◽  
Recoil Effect ◽  
Buffer Solution ◽  
Suitable Alternative ◽  
Detailed Chemistry ◽  
Mild Conditions ◽  
Radiochemical Yields ◽  
The Stability ◽  
High Yields

Background: Synthesis of 225Actinium derivatives using PSMA-617, DOTATATE peptides and EDTMP ligand was afforded. Detailed experimental, quality control (QC) and stability studies were well described. The radiolabelling reactions were performed in mild conditions with desirable radiochemical yields and high radiochemical purities. Methods: PSMA-617, and DOTATATE were radiolabelled with 225Actinium in 0.1 M HCl in the presence of ascorbate buffer solution and passed through the C-18 light cartridge for purification and the product was eluted by ethanol-water solution. EDTMP was also radiolabelled with 225Actinium without using any stabilizer and purification step. All products were well analyzed by R-TLC and R-HPLC. The stability of those compounds was also studied within the valid time. Results: 225Ac-DOTATATE and 225Ac-PSMA-617 were obtained at the same condition. The radiochemical yield of 225Ac-DOTATATE was less than 225Ac-PSMA 617. Stability experiments indicated decay daughters of 225Actinium appeared after T0 +1 h due to the recoil effect radiolysis. On the other hand, 225Ac-EDTMP was more stable than DOTA-peptide radiolabelled compounds. 225Ac-EDTMP was produced with more than 95% radiochemical yield and 99% radiochemical purity. Conclusion: A detailed chemistry study was presented for the synthesis of 225Actinium derivatives in mild conditions with absolute radiochemical purities and high yields. Experimental results showed that 225Ac-EDTMP could be a suitable alternative radiopharmaceutical for bone metastases arising from primer tumors as a cocktail therapy.

scholarly journals Stability of Principal Hydrolysable Tannins from Trapa taiwanensis Hulls

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 365 ◽  
Author(s):  
Ching-Chiung Wang ◽  
Hsyeh-Fang Chen ◽  
Jin-Yi Wu ◽  
Lih-Geeng Chen
Keyword(s):  
Protective Effect ◽  
Water Solution ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Intestinal Fluid ◽  
Buffer Solution ◽  
Simulated Intestinal Fluid ◽  
Hydrolysable Tannins ◽  
The Stability ◽  
Tellimagrandin Ii

The fruit and hulls of the water caltrop (Trapa taiwanensis Nakai) are used as hepatoprotective herbal tea ingredients in Taiwan. The stability of hydrolysable tannins in herbal drinks has rarely been reported. In the present study, two hydrolysable tannins, tellimagrandin II (TGII) and 1,2,3,4,6-pentagalloylglucopyranose (PGG), were isolated from water caltrop hulls. The stability of the two compounds was evaluated by treatment with various pH buffer solutions, simulated gastric fluid and intestinal fluid, different temperatures, and photo-irradiation at 352 nm in different solvents. Results showed that TGII and PGG were more stable in a pH 2.0 buffer solution (with 91.88% remaining) and in a water solution with 352 nm irradiation (with 95% remaining). TGII and PGG were more stable in methanol or ethanol solutions (with >93.69% remaining) than in an aqueous solution (with <43.52% remaining) at 100 °C. In simulated gastric fluid, more than 96% of the hydrolysable tannins remained after incubation at 37 °C for 4 h. However, these hydrolysable tannins were unstable in simulated intestinal fluid, as after incubation at 37 °C for 9 h, the content of TGII had decreased to 31.40% and of PGG to 12.46%. The synthetic antioxidants, butyl hydroxy anisole (BHA), di-butyl hydroxy toluene (BHT), and propyl gallate, did not exhibit photoprotective effects on these hydrolysable tannins. However, catechin, a natural antioxidant, displayed a weak photoprotective effect. Ascorbic acid had a short-term thermal-protective effect but not a long-term protective effect. The different stability properties of hydrolysable tannins in solutions can be used in the development of related herbal teas in the future.

scholarly journals Re-Evaluations of Zr-DFO Complex Coordination Chemistry for the Estimation of Radiochemical Yields and Chelator-to-Antibody Ratios of 89Zr Immune-PET Tracers

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4977
Author(s):  
Ryota Imura ◽  
Hiroyuki Ida ◽  
Ichiro Sasaki ◽  
Noriko S. Ishioka ◽  
Shigeki Watanabe
Keyword(s):  
Monoclonal Antibody ◽  
Stability Constants ◽  
Chemical Species ◽  
Radiochemical Yield ◽  
Unknown Species ◽  
Radiochemical Yields ◽  
The Stability ◽  
Complex Coordination ◽  
Antibody Ratio ◽  
Good Agreement

(1) Background: Deferoxamine B (DFO) is the most widely used chelator for labeling of zirconium-89 (89Zr) to monoclonal antibody (mAb). Despite the remarkable developments of the clinical 89Zr-immuno-PET, chemical species and stability constants of the Zr-DFO complexes remain controversial. The aim of this study was to re-evaluate their stability constants by identifying species of Zr-DFO complexes and demonstrate that the stability constants can estimate radiochemical yield (RCY) and chelator-to-antibody ratio (CAR). (2) Methods: Zr-DFO species were determined by UV and ESI-MS spectroscopy. Stability constants and speciation of the Zr-DFO complex were redetermined by potentiometric titration. Complexation inhibition of Zr-DFO by residual impurities was investigated by competition titration. (3) Results: Unknown species, ZrHqDFO2, were successfully detected by nano-ESI-Q-MS analysis. We revealed that a dominant specie under radiolabeling condition (pH 7) was ZrHDFO, and its stability constant (logβ111) was 49.1 ± 0.3. Competition titration revealed that residual oxalate inhibits Zr-DFO complex formation. RCYs in different oxalate concentration (0.1 and 0.04 mol/L) were estimated to be 86% and >99%, which was in good agreement with reported results (87%, 97%). (4) Conclusion: This study succeeded in obtaining accurate stability constants of Zr-DFO complexes and estimating RCY and CAR from accurate stability constants established in this study.

scholarly journals Electrochemical multicomponent synthesis of 4-selanylpyrazoles under catalyst- and chemical-oxidant-free conditions

2021 ◽  
Author(s):  
Yan Wu ◽  
Jin-Yang Chen ◽  
Jing Ning ◽  
Xue Jiang ◽  
Jie Deng ◽  
...  
Keyword(s):  
Multicomponent Reaction ◽  
Raw Materials ◽  
Multicomponent Synthesis ◽  
Mild Conditions ◽  
Simple Protocol ◽  
High Yields

An electrochemical multicomponent reaction was established under catalyst-, chemical-oxidant-free and mild conditions, which provides an eco-friendly and simple protocol for constructing 4-selanylpyrazoles from easily available raw materials with high yields.

scholarly journals Improved synthesis of SV2A targeting radiotracer [11C]UCB-J

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Johanna Rokka ◽  
Eva Schlein ◽  
Jonas Eriksson
Keyword(s):  
Methyl Iodide ◽  
Water Solution ◽  
Synthesis Method ◽  
Radiochemical Yield ◽  
Preparative Hplc ◽  
Step Method ◽  
Synaptic Density ◽  
Excellent Starting Point ◽  
Starting Point

Abstract Introduction [11C]UCB-J is a tracer developed for PET (positron emission tomography) that has high affinity towards synaptic vesicle glycoprotein 2A (SV2A), a protein believed to participate in the regulation of neurotransmitter release in neurons and endocrine cells. The localisation of SV2A in the synaptic terminals makes it a viable target for in vivo imaging of synaptic density in the brain. Several SV2A targeting compounds have been evaluated as PET tracers, including [11C]UCB-J, with the aim to facilitate studies of synaptic density in neurological diseases. The original two-step synthesis method failed in our hands to produce sufficient amounts of [11C]UCB-J, but served as an excellent starting point for further optimizations towards a high yielding and simplified one-step method. [11C]Methyl iodide was trapped in a clear THF-water solution containing the trifluoroborate substituted precursor, potassium carbonate and palladium complex. The resulting reaction mixture was heated at 70 °C for 4 min to produce [11C]UCB-J. Results After semi-preparative HPLC purification and reformulation in 10% ethanol/phosphate buffered saline, the product was obtained in 39 ± 5% radiochemical yield based on [11C]methyl iodide, corresponding to 1.8 ± 0.5 GBq at EOS. The radiochemical purity was > 99% and the molar activity was 390 ± 180 GBq/μmol at EOS. The product solution contained < 2 ppb palladium. Conclusions A robust and high yielding production method has been developed for [11C]UCB-J, suitable for both preclinical and clinical PET applications.

scholarly journals Nanotechnology-based approaches for targeting and delivery of drugs via Hexakis (m-PE) macrocycles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samaneh Pasban ◽  
Heidar Raissi
Keyword(s):  
Drug Delivery ◽  
Density Functional ◽  
Water Solution ◽  
Decomposition Analysis ◽  
Binding Energies ◽  
Energy Decomposition Analysis ◽  
Partial Density ◽  
High Propensity ◽  
The Stability ◽  
Novel Applications

AbstractHexakis (m-phenylene ethynylene) (m-PE) macrocycles, with aromatic backbones and multiple hydrogen-bonding side chains, had a very high propensity to self-assemble via H-bond and π–π stacking interactions to form nanotubular structures with defined inner pores. Such stacking of rigid macrocycles is leading to novel applications that enable the researchers to explored mass transport in the sub-nanometer scale. Herein, we performed density functional theory (DFT) calculations to examine the drug delivery performance of the hexakis dimer as a novel carrier for doxorubicin (DOX) agent in the chloroform and water solvents. Based on the DFT results, it is found that the adsorption of DOX on the carrier surface is typically physisorption with the adsorption strength values of − 115.14 and − 83.37 kJ/mol in outside and inside complexes, respectively, and so that the essence of the drug remains intact. The negative values of the binding energies for all complexes indicate the stability of the drug molecule inside and outside the carrier's cavities. The energy decomposition analysis (EDA) has also been performed and shown that the dispersion interaction has an essential role in stabilizing the drug-hexakis dimer complexes. To further explore the electronic properties of dox, the partial density of states (PDOS and TDOS) are calculated. The atom in molecules (AIM) and Becke surface (BS) methods are also analyzed to provide an inside view of the nature and strength of the H-bonding interactions in complexes. The obtained results indicate that in all studied complexes, H-bond formation is the driving force in the stabilization of these structures, and also chloroform solvent is more favorable than the water solution. Overall, our findings offer insightful information on the efficient utilization of hexakis dimer as drug delivery systems to deliver anti-cancer drugs.

scholarly journals GMP production of 6-[18F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Valdemar L. Andersen ◽  
Mikkel A. Soerensen ◽  
Johan Hygum Dam ◽  
Niels Langkjaer ◽  
Henrik Petersen ◽  
...  
Keyword(s):  
Radiochemical Yield ◽  
Ct Imaging ◽  
University Hospital ◽  
Dopamine Synthesis ◽  
Congenital Hyperinsulinism ◽  
Molar Activity ◽  
Time Period ◽  
Pet Ct ◽  
Synthetic Routes ◽  
Radiochemical Yields

Abstract Background The radiofluorinated levodopa analogue 6-[18F]F-l-DOPA (3,4-dihydroxy-6-18F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [18F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site. Methods Data from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed. Results The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants. Conclusion For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.

scholarly journals New Spectrophotometric Method for Determination of Cadmium

2009 ◽  
Vol 6 (s1) ◽  
pp. S496-S500
Author(s):  
K. S. Parikh ◽  
R. M. Patel ◽  
K. N. Patel
Keyword(s):  
Stability Constant ◽  
Spectrophotometric Method ◽  
Basic Medium ◽  
Buffer Solution ◽  
Solution Ph ◽  
Yellow Colour ◽  
Maximum Absorbance ◽  
The Stability

The reagent 2-hydroxy-4-n-butoxy-5-bromopropiophenone thiosemicarbazone (HBBrPT) has been used for the determination of Cd(II) by using spectrophotometric method. The reagent HBBrPT gave an intense yellow colour with Cd(II) solution in basic medium. The maximum absorbance was observed at 440 nm, in basic buffer solution (pH 10.00). The molor absorptivity and Sandell’s sensitivity of Cd(II)-HBBrPT complex were 4035 mol-1cm-1and 0.02765 μg cm-2respectively. The stability constant of 1:2 Cd(II)-HBBrPT complex was 8.46×106. The effect of various iron was also studied.

scholarly journals Evaluation of Lipases from Wild Microbial Strains as Biocatalysts in Biodiesel Production

Separations ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 53 ◽  
Author(s):  
Carlos Luna ◽  
Diego Luna ◽  
Felipa Bautista ◽  
Juan Calero ◽  
Antonio Romero ◽  
...  
Keyword(s):  
Biodiesel Production ◽  
Purification Process ◽  
Bacterial Strains ◽  
Production Methods ◽  
Mild Conditions ◽  
New Type ◽  
Microbial Strains ◽  
The Stability ◽  
Microbial Strain ◽  
Biodiesel Industry

In this study, the evaluation of the catalytic behavior of several wild bacterial strains in the 1,3-selective ethanolysis of triglycerides with ethanol to produce a new type of biodiesel (Ecodiesel) that integrates glycerol as monoacylglycerols was carried out. The Ecodiesel production not only avoids the elimination of glycerol, which is largely generated as a by-product in the biodiesel industry, but also results in an increase in the biofuel yield. The wild microbial strain samples were obtained from several lipophilic organisms. In addition to evaluate the enzymatic extracts, the minimum grade of purification of the strains, necessary to obtain similar results to those attained with commercial lipases was studied. This purification treatment included a dialysis followed by a lyophilization process. Such extracts were directly used as biocatalysts in the transesterification reaction of sunflower oil with ethanol, attaining much better results (yield close to 100%) than those obtained with strains which were not submitted to the purification process (yields lower than 10%). Furthermore, the results here obtained are similar to those obtained with commercial lipases but were achieved under mild conditions and lower reaction time (2 h). In addition, the stability of the enzymatic extracts was corroborated by subsequent reactions, showing no loss of activity. Thus, this study brings to light that enzymatic extracts obtained by a very simple purification process can be economically competitive with the conventional biodiesel production methods.

scholarly journals Scalable 18F Processing Conditions for Copper-Mediated Radiofluorination Chemistry Facilitate "Design of Experiments" (DoE) Optimization Studies and Afford an Improved Synthesis of [18F]Olaparib.

2021 ◽  
Author(s):  
Gregory D. Bowden ◽  
Nantanat Chailanggar ◽  
Bernd J. Pichler ◽  
Andreas Maurer
Keyword(s):  
Design Of Experiments ◽  
Radiochemical Yield ◽  
Small Scale ◽  
Processing Conditions ◽  
Single Production ◽  
Activity Yield ◽  
Radiochemical Yields ◽  
Parp 1 ◽  
18F Fluoride

A convenient, scalable, and azeotropic drying free method for processing [18F]fluoride as base free<br>[18F]TBAF is reported and applied to copper-mediated radiofluorination (CMRF) radiosyntheses. A central<br>feature of this method is that a single production of [18F]TBAF can be divided into small aliquots that can be<br>used to perform multiple small-scale reactions in DoE optimization studies. The results of these studies can<br>then be reliably translated to full batch tracer productions using automated synthesizers. This processing<br>technique was successfully applied to the manual DoE optimization, DoE study validation, and subsequent<br>full-batch automation of the PARP-1 tracer [18F]olaparib. After DoE optimization, we were able to produce<br>[18F]olaparib in high radiochemical yields via both manual (%RCY (CMRF step only) = 78 ± 6 %, n = 4) and<br>automated (up to 80% radiochemical yield (%RCY); 41% activity yield (%AY)) radiosynthesis procedures.<br>This work further demonstrates the power of the DoE approach for improving the radiochemical yields and<br>radiosynthesis performance of clinically relevant tracer productions

scholarly journals Color Stability of Phycoerythrin Crude Extract (PECE) from Rhodomonas Salina Toward Physicochemical Factors

2019 ◽  
Vol 14 (1) ◽  
pp. 21
Author(s):  
Endar Marraskuranto ◽  
Tri Joko Raharjo ◽  
Rina Sri Kasiamdari ◽  
Tri Rini Nuringtyas
Keyword(s):  
Phosphate Buffer Solution ◽  
Color Stability ◽  
Ethanol Solution ◽  
Future Application ◽  
Buffer Solution ◽  
Solution Ph ◽  
Rhodomonas Salina ◽  
Freeze Dried ◽  
Physicochemical Factors ◽  
The Stability

Rhodomonas salina produces Cr-phycoerythrin545 as its designated phycoerythrin (PE) with an absorption maximum at 545 nm and a shoulder 564 nm. PE has potential to be applied as colorants, pharmaceutical agents, and fluorescent dye tags. The stability of the PE color is influenced by the physicochemical factors of the solution. This study aimed to analyze the color stability of PECE against chemical (ethanol and pH) and physical (light and temperature) factors. PECE was prepared from freeze-dried biomass of R. salina and was extracted in phosphate buffer solution (pH = 6.0) using a freeze-thaw method in -25 oC (2 hours) and 4 oC (24 hours). The resulting extract was concentrated and dried in a freeze-dryer. Analyses were conducted using UV-visible and fluorescence spectrophotometer. PECE showed color stability against light of white fluorescent lamp exposure up to 8 hours, temperature exposure up to 40 oC, ethanol solution up to concentration of 20 % (v/v), and pH range 3.9-8.42. Results from this study can be useful for extraction, purification, and future application of Cr-PE545.

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