Synthesis of 16-Epiestriol and its Radiolabeling Procedure

To explore novel synthetic routes of 16-epiestriol (Estra-1, 3, 5(10)-triene-3, 16β, 17β-triol), we used the estrone as the starting material. After some simple synthetic steps, 16-epiestriol was yielded. Identification and purity of intermediates in the synthetic routes were characterized by melting point and ¹H NMR spectrum analysis, respectively. In addition, the structure of 16-epiestriol was modified and radiolabeled with¹⁸F-fluoride to yield¹⁸F-FES. The corresponding quality control analysis of the injection were performed. The yield of two synthetic routes of 16-epiestriol were about 20% starting from estrone. Radiosynthesis of¹⁸F-FES was finished in 60 minutes with a radiochemical yield of (30±4)% and radiochemical purity greater than 99%. The¹⁸F-FES injection was colorless and clear and the pH value was 6.5-7.5. The specific activity of the injection saline was (1.75±0.25) Ci/μmol. In this study, 16-Epiestriol was yielded with a relatively high yield in two novel routes.¹⁸F-FES was finally yielded after structure modification of 16-epiestriol and the corresponding radiolabeling procudure. The quality control results of the¹⁸F-FES injection could meet the need in clinical examination.     

A New SiF–Dipropargyl Glycerol Scaffold as a Versatile Prosthetic Group to Design Dimeric Radioligands: Synthesis of the [18F]BMPPSiF Tracer to Image Serotonin Receptors

A novel SiX–dipropargyl glycerol scaffold (X: H, F, or ¹⁸F) was developed as a versatile prosthetic group that provides technical advantages for the preparation of dimeric radioligands based on silicon fluoride acceptor pre‐ or post‐labeling with fluorine‐18. Rapid conjugation with the prosthetic group takes place in microwave‐assisted click conjugation under mild conditions. Thus, a bivalent homodimeric SiX–dipropargyl glycerol derivatized radioligand, [¹⁸F]BMPPSiF, with enhanced affinity was developed by using click conjugation. High uptake of the radioligand was demonstrated in 5‐HT_1A receptor‐rich regions in the brain with positron emission tomography. Molecular docking studies (rigid protein–flexible ligand) of BMPPSiF and known antagonists (WAY‐100635, MPPF, and MefWAY) with monomeric, dimeric, and multimeric 5‐HT_1A receptor models were performed, with the highest G score obtained for docked BMPPSiF: ?6.766 as compared with all three antagonists on the monomeric model. Multimeric induced‐fit docking was also performed to visualize the comparable mode of binding under in vivo conditions, and a notably improved G score of ?8.455 was observed for BMPPSiF. These data directly correlate the high binding potential of BMPPSiF with the bivalent binding mode obtained in the biological studies. The present study warrants wide application of the SiX–dipropargyl glycerol prosthetic group in the development of ligands for imaging with enhanced affinity markers for specific targeting based on peptides, nucleosides, and lipids.     

18F-FDG的放射性标记、显像原理与临床研究进展

PET/CT是当今最先进的诊断技术之一,实现了解剖学影像与功能学影像的融合。¹⁸F-FDG是最为重要的正电子药物,其使用量占全部PET/CT显像的95%以上。FDG-PET已经广泛应用于诊断肿瘤、心脏病和癫痫等多种疾病。本文回顾了¹⁸F-FDG的发展历史,介绍了¹⁸F-FDG的制备与质量控制,分析了¹⁸F-FDG显像原理,阐述了FDG-PET等临床应用研究进展。     

A study on indirect radiolabeling of IgG with carrier free ~(188)Re

188Re labeled monoclonal antibodies are potential candidates for use in radioimmunotherapy. S-Bz-MAG3 as a bifunctional chelating agent was used for labeling of IgG with carrier free 188Re by pre-radiolabel-ing of the chelating approach. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results may be useful to the studies of 188Re labeled MAbs for radioimmunotherapy.     

Polydopamine as a Biocompatible Multifunctional Nanocarrier for Combined Radioisotope Therapy and Chemotherapy of Cancer

Development of biodegradable nanomaterials for drug delivery and cancer theranostics has attracted great attention in recent years. In this work, polydopamine (PDA), a biocompatible polymer, is developed as a promising carrier for loading of both radionuclides and an anticancer drug to realize nuclear‐imaging‐guided combined radioisotope therapy (RIT) and chemotherapy of cancer in one system. It is found that PDA nanoparticles after modification with poly(ethylene glycol) (PEG) can successfully load several different radionuclides such as ^99mTc and ¹³¹I, as well as an anticancer drug doxorubicin (DOX). While labeling PDA‐PEG with ^99mTc (^99mTc‐PDA‐PEG) enables in vivo single photon emission computed tomography imaging, nanoparticles co‐loaded with ¹³¹I and DOX (¹³¹I‐PDA‐PEG/DOX) can be utilized for combined RIT and chemotherapy, which offers effective cancer treatment efficacy in a remarkably synergistic manner, without rendering significant toxicity to the treated animals. Therefore, this study presents an interesting class of biocompatible nanocarriers, which allow the combination of RIT and chemotherapy, the two extensively applied cancer therapeutic strategies, promising for future clinic translations in cancer treatment.     

Synthesis of a Bifunctional Cross-Bridged Chelating Agent,Peptide Conjugation,and Comparison of 68Ga Labeling and Complex Stability Characteristics with Established Chelators

[⁶⁸Ga]Ga³⁺ can be introduced into receptor-specific peptidic carriers via different chelators to obtain radiotracers for Positron Emission Tomography imaging and the chosen chelating agent considerably influences the in vivo pharmacokinetics of the corresponding radiopeptides. A chelator that should be a valuable alternative to established chelating agents for ⁶⁸Ga-radiolabeling of peptides would be a backbone-functionalized variant of the chelator CB-DO2A. Here, the bifunctional cross-bridged chelating agent CB-DO2A-GA was developed and compared to the established chelators DOTA, NODA-GA and DOTA-GA. For this purpose, CB-DO2A-GA(tBu)₂ was introduced into the peptide Tyr³-octreotate (TATE) and in direct comparison to the corresponding DOTA-, NODA-GA-, and DOTA-GA-modified TATE analogs, CB-DO2A-GA-TATE required harsher reaction conditions for ⁶⁸Ga-incorporation. Regarding the hydrophilicity profile of the resulting radiopeptides, a decrease in hydrophilicity from [⁶⁸Ga]Ga-DOTA-GA-TATE (log_D(7.4) of −4.11±0.11) to [⁶⁸Ga]Ga-CB-DO2A-GA-TATE (−3.02±0.08) was observed. Assessing the stability against metabolic degradation and complex challenge, [⁶⁸Ga]Ga-CB-DO2A-GA demonstrated a very high kinetic inertness, exceeding that of [⁶⁸Ga]Ga-DOTA-GA. Therefore, CB-DO2A-GA is a valuable alternative to established chelating agents for ⁶⁸Ga-radiolabeling of peptides, especially when the formation of a very stable, positively charged ⁶⁸Ga-complex is pursued.     

Strategies to determine the molecular basis of chemical communication by trematodes

The identification of pheromones and chemicals that may inhibit or stimulate growth and reproduction necessarily leads to the consideration of biochemical methods to isolate and characterize these molecules. Analysis ofSchistosoma mansoni surface antigens by direct radioiodination, metabolic labeling with tritiated and¹⁴C-tagged hexose precursors, affinity chromatography, isoelectric focusing, hydrophobic chromatography, and competitive inhibition is presented to illustrate methods of immunochemical analysis and antigen purification. Technical problems that may arise when investigating parasite molecular biology are described. Evidence of diminished fecundity of female worms in acutely infected mice supports the theory of a crowding effect in murine schistosomiasis and suggests the possibility that worm secretions or metabolites may function as chemical messages to inhibit oviposition. There is also evidence that the immune response of mice to an isolated surface antigen from adult worms results in the attenuation of hepatic granulomata of challenge infections. Several hypotheses are proposed to elucidate the molecular basis for chemical communication between trematodes and analytical approaches to test these hypotheses are outlined.The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Animal Resources, National Research Council, DHEW Pub. No. (NIH) 78-23.     

Improved preparation and chemical kinetics on fully automated synthesis of [18F]-THK523,a PET imaging probe for Tau pathologies

Extensive accumulation of neurofibrillary tangles(NFTs)consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer's disease.However,no PET probe is currently available for selective detection of NFTs in the living human brain.[~(18)F]-THK523 was developed as a potential in vivo imaging probe for tau pathology.In this paper,we report a new protected precursor,2-((2-(4-((tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(THK-7),instead of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[~(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[~(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[~(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.