Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals

Metallic radionuclides are the mainstay of both diagnostic and therapeutic radiopharmaceuticals. Therapeutic nuclear medicine is less advanced but has tremendous potential if the radionuclide is accurately targeted. Great interest exists in the field of inorganic chemistry for developing target specific radiopharmaceuticals based on radiometals for non-invasive disease detection and cancer radiotherapy. This perspective will focus on the nuclear properties of a few important radiometals and their recent applications to developing radiopharmaceuticals for imaging and therapy. Other topics for discussion will include imaging techniques, radiotherapy, analytical techniques, and radiation safety. The ultimate goal of this perspective is to introduce inorganic chemists to the field of nuclear medicine and radiopharmaceutical development, where many applications of fundamental inorganic chemistry can be found.     

Radiohalogens for imaging and therapy

Radiohalogens play a very important role in radiopharmaceuticals used for medical imaging (now referred to as molecular imaging) and therapy applications. Development of new radiopharmaceuticals that have radiohalogens incorporated requires an understanding of parameters that are unique to chemistry involving these radionuclides. Those parameters include requirement for production and purification of the halogen radionuclides, as well as development of reaction conditions for use with high specific activity short-lived radionuclides. In this tutorial review, several radiohalogens, their radiolabeling chemistry and their application to medical imaging and therapy are discussed.     

Nanocompatible chemistry toward fabrication of target-specific gold nanoparticles

Nanocompatible chemistry which utilizes a novel nontoxic phosphino amino acid as a reducing agent has resulted in the development of therapeutically useful gold nanoparticles under biologically benign media. Stabilization of gold nanoparticles by the edible gum arabic matrix has provided an effective pathway toward in vivo stable target-specific gold nanoparticles.     

Ether and crown ether-containing cationic 99mTc complexes useful as radiopharmaceuticals for heart imaging

While radiopharmaceutical research has been focused on the development of target-specific radiotracers for early detection and radiotherapy of cancers in the last decade, there is a limited effort on new cationic 99mTc radiotracers for heart imaging. This review will summarize some of the most recent developments in ether- and crown ether-containing cationic 99mTc radiotracers that have a fast liver clearance with a heart/liver ratio substantially better than that of 99mTc-Sestamibi and 99mTc-Tetrofosmin, the two commercial 99mTc radiopharmaceuticals currently available for myocardial perfusion imaging. Fast liver clearance might shorten the duration of imaging protocols (<30 min post-injection), and allow for early acquisition of heart images of high quality. Improvement of heart/liver ratio may permit better detection of the presence and extent of coronary artery disease. Identification of such a new radiotracer that allows for the improved non-invasive delineation of myocardial perfusion would be of considerable benefit in treatment of patients with suspected coronary artery disease.     

核化学与放射化学的研究进展

在我国核能快速发展的新形势下,新型核能资源的开发、乏燃料后处理、放射性废物处理与处置等核燃料循环化学研究日益活跃。随着科学技术的不断发展,离子加速器、反应堆、各种类型的探测器和分析设备、以及计算机技术等的发展,核化学与放射化学研究的范围和成果在不断扩展和增加,如核安全、环境放射化学、放射分析化学、放射性药物与标记化合物等,研究成果对于国防建设、核能发展、核技术应用等方面具有重要支撑作用。本文综述了近年来国内在上述领域所取得的研究进展。共引用参考文献161篇。     

64Cu放射性药物化学

64Cu半衰期为12.7 h,其衰变过程既发射β+粒子(β+,0.655 MeV,17.8%),又发射β-粒子(β-,0.573 MeV,38.4%)。近20年来,随着铜配位化学的发展,新型配体不断出现(如DOTA、TETA、NOTA、CB-TE2A、C3B-DO2A等)。Cu(Ⅱ)的络合物在生物体内/外的稳定性不断提高,64Cu已经成功标记在氨基酸、多肽、蛋白、核酸等分子以及纳米颗粒上。64Cu可制成正电子显像药物用作诊断,同时也有发展为放射性治疗药物的潜力。新型铜配体和标记方法以及新的药物靶标的研究已经成为64Cu放射性药物研究的热点,至今已研制出了多种64Cu标记的放射性药物,如64Cu-ATSM是有效的肿瘤乏氧显像剂,64Cu-PTSM是优良的血流示踪剂等。本文旨在介绍64Cu(Ⅱ)几种主要类型的含氮配体以及64Cu标记的放射性药物在显像和治疗方面的最新研究进展,并展望其发展趋势。     

Towards molecular imaging and treatment of disease with radionuclides: the role of inorganic chemistry

Molecular imaging and radiotherapy using radionuclides is a rapidly expanding field of medicine and medical research. This article highlights the development of the role of inorganic chemistry in designing and producing the radiopharmaceuticals on which this interdisciplinary science depends.     

99mTc放射性药物中的配位化学

在99mTc间接标记放射性药物中双功能螯合剂起到重要的连接作用,其在很大程度上决定了放射性药物的理化性质。99mTc标记放射性药物中常用的双功能螯合剂大都含有N、S、P等杂原子,本文以与锝核配位杂原子的不同对双功能螯合剂进行分类,分别对NxS(4-x)型配体、“3＋1”混合配体、含膦配体以及以[99mTc(CO)3]+为配位中心的99mTc放射性药物逐一进行介绍。     

A review on <Superscript>90</Superscript>Y-labeled compounds and biomolecules

The field of therapeutic nuclear medicine is emerging rapidly as choice of treatment in oncology and other cellular malignancies. The growth of this branch of nuclear medicine is greatly facilitated by the introduction of a number of new radiopharmaceuticals and radionuclides. ⁹⁰Y-radiopharmaceuticals have confirmed their worth in medical and clinical areas in a very short span of time. The ⁹⁰Y is a radioisotope widely used for therapeutic purposes and considerable perfection has been made to understand the chemistry of ⁹⁰Y-labeled radiopharmaceuticals. The development of these radiopharmaceuticals can be made favorable by using appropriate buffer, incubation period, optimal pH, specific activity and reaction temperature. In this review, we have discussed the preparation of range of ⁹⁰Y transporting biological molecules such as antibodies radiolabeled peptides, antigens and microsphere with their clinical applications.     

The role of coordination chemistry in the development of copper and rhenium radiopharmaceuticals

There are several isotopes of copper and rhenium that are of interest in the development of new molecular imaging or radiotherapeutic agents. This perspective article highlights the role of coordination chemistry in the design of copper and rhenium radiopharmaceuticals engineered to selectively target tissue of interest such as cancer cells or pathological features associated with Alzheimer's disease. The coordination chemistry of copper bis(thiosemicarbazone) derivatives and copper macrocyclic complexes is discussed in terms of their potential application as targeted positron emission tomography tracers for non-invasive diagnostic imaging. A range of rhenium complexes with different ligands with rhenium in different oxidation states are introduced and their potential to be translated to new radiotherapeutic agents discussed.     

Paper chromatographic and paper elettrophoretic study of the solution chemistry of Tc-99m-methylendiphosphonate and of Tc-99m-dimercaptosuccinate for improving the tumour-affinity of Tc-99m during scintigraphic imaging of cancer

In order to find the conditions under which Tc-99m-methylenediphosphonate (Tc-99m-MDP) and Tc-99m(V)-dimercaptosuccinate (Tc-99m(V)-DMSA) may become tumour-seeking agents, leaving healthy organs free from the radionuclide uptake, the solution chemistry of these radiopharmaceuticals was studied by paper chromatography and paper electrophoresis in distilled water, in physiological saline, in NAHCO3, and ascorbic acid solutions. Both radiopharmaceuticals are anionic in the radiopharmaceutical solution but get easily hydrolysed to form cationic Tc-99m species which concentrates in healthy bone and in some bone metastases. Tc-99m (V)-DMSA being more stable remains long in the blood pool giving undesirable presence of the radionuclide in lung, heart and kidneys, in addition to its reduced uptake in bone metastases and in some primaries. We are trying to eliminate these drawbacks of healthy organ uptake of Tc-99-m(V)-DMSA not only to get a clean scintigraphic image of the tumour with this radiopharmaceutical but to extend its formulation, thus obtained, to prepare radiopharmaceutical with Re-188, which is the higher homologue of Tc-99m, for systemic therapy of cancer. Essentially similar solution chemistry of both radiopharmaceuticals suggests that like Tc-99m-MDP, technetium-99m-dimercaptosuccinate is also a complex of tetravalent Tc-99m and not of pentavalent Tc-99m as so far supposed to be.     

Convenient route leading to neutral fac-M(CO)3(NNO) complexes (M = Re, 99mTc) coupled to amine pharmacophores

The synthesis and characterization of three neutral tricarbonyl fac-M(CO)3(NNO) (M = Re, (99m)Tc) complexes based on the picolylamine N,N-diacetic acid (PADA) ligand is reported. One of the two carboxylate groups of the PADA ligand is efficiently and conveniently derivatized with an amine nucleophile through the use of the PADA anhydride. In this work, aniline, benzylamine and pyrrolidine were used as model amine nucleophiles. The rhenium complexes were synthesized using the [NEt4]2[Re(CO)3Br3] precursor and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. The analogous technetium-99m complexes were also prepared quantitatively using the [(99m)Tc(CO)3(H2O)3](+) precursor. The reaction scheme presented for the synthesis of the fac-M(CO)3(NNO) (M = Re, (99m)Tc) complexes can be applied to the development of target-specific radiopharmaceuticals because, in principle, any bioactive pharmacophore bearing an amine group can be used in the place of the model amine nucleophiles.     

From organometallic and polymer chemistry to applied materials science: transition metal catalyzed synthesis of polyolefins and polyolefin-based high-performance materials

A brief history of the development of transition metal-catalyzed olefin polymerization including the present status of polyolefin chemistry is given. The entire evolution of polyolefin chemistry will be outlined, giving ample attention to the development in the catalytic systems. Starting with the first generation PP catalysts (TiCl₃/AlClEt₂), the success story of organometallic chemistry, which resulted in modern supported and unsupported single site systems and finally functional group-tolerant group VIII systems will be summarized. Where applicable, examples of technical application will be given. Additionally, organometallic chemistry responsible for selectivity but also for termination reactions as well as the various “living” systems and the adherent implications for materials science will be discussed. Finally, the impact of related transition metal-catalyzed metathesis chemistry on the area of specialty materials will be outlined.     

Target-Specific Bioorthogonal Reactions for Precise Biomedical Applications

Bioorthogonal chemistry is a promising toolbox for dissecting biological processes in the native environment. Recently, bioorthogonal reactions have attracted considerable attention in the medical field for treating diseases, since this approach may lead to improved drug efficacy and reduced side effects via in situ drug synthesis. For precise biomedical applications, it is a prerequisite that the reactions should occur in the right locations and on the appropriate therapeutic targets. In this minireview, we highlight the design and development of targeted bioorthogonal reactions for precise medical treatment. First, we compile recent strategies for achieving target-specific bioorthogonal reactions. Further, we emphasize their application for the precise treatment of different therapeutic targets. Finally, a perspective is provided on the challenges and future directions of this emerging field for safe, efficient, and translatable disease treatment.     

SAR studies of quinoline and derivatives as potential treatments for Alzheimer’s disease

Quinoline analogs are an important class of N-based heterocyclic compounds, which have received extensive attention because of their use in medicinal chemistry and organic synthesis. Over the past few decades, several new scaffold-based functionalization synthesis strategies have been reported for quinolines. Quinoline derivatives have a wide range of biological activities, including anti-Alzheimer’s disease activity. Herein, we review research on quinoline and related analogs as anti-Alzheimer’s disease agents from 2001 to 2022 and particularly highlight the structure–activity relationships and molecular binding modes. This review provides information for the rational design of more effective and target-specific drugs for Alzheimer's disease.     

Synthesis of C-11 and F-18 labelled compounds for biomedical applications: Current status and challenges for the future

The synthesis of¹¹C and¹⁸F labelled compounds for biomedical applications is a rapidly growing field with applications in Neurology, Cardiology, Oncology and the study of human biochemistry and physiology. Literally hundreds of compounds have been labelled but only a few have made their way into human studies with the bulk being used in animal studies. This review focuses on the production of these isotopes, the chemistry of labelling radiopharmaceuticals with these isotopes, automated chemistry and finally future considerations and applications for both¹¹C and¹⁸F.     

胶体与界面化学的研究进展

胶体与界面化学是研究胶体分散体系和界面现象的一门科学,在能源、材料、生物、化学制造和环境科学等领域具有广泛的应用。近年来,由于先进功能材料、仿生学和生物医药等学科的迅速发展,在纳米尺寸(胶体)的范围内进行分子组装和材料的制备已经引起了人们的高度关注。过去两年里,中国胶体与界面化学领域的科学家的创新性研究工作层出不穷,国际影响力日益提升,所获得的研究成果越来越受到国际同行的关注。这些成果可概括为:(1)系列新型有序分子组合体的构建及其在生物医药领域的应用,尤其是超分子组装、表面图案化有序组装材料的设计和应用;(2)胶体与界面化学方法在微纳米功能材料合成中的应用,包括形貌可控的无机材料、有机-无机复合功能材料、贵金属纳米材料以及小分子凝胶的合成及其应用;(3)胶体与界面化学在生物传感领域的新应用;(4)胶体与界面化学研究新方法。作为一门与实际应用密切结合的学科,现代经济社会为胶体与界面化学的发展提供了广阔的空间。可以预期,未来胶体与界面化学将更注重其基本的物理化学问题,如:新颖有序分子组合体的构建和理论认识;功能性微纳米材料界面结构与性能调控的理论指导。此外,新的手段和方法在胶体与界面体系的不断渗透,将不断产生新的学科交叉点,从而有力地促进胶体与界面化学的学科发展。共引用参考文献96篇。     

From conventional to unusual enzyme inhibitor scaffolds: the quest for target specificity

The tremendous challenge presented by the specific molecular recognition of single biomacromolecular targets within complex biological systems demands novel and creative design strategies. This Minireview discusses some conventional and unusual approaches for the design of target-selective enzyme inhibitors with a focus on the underlying chemical scaffolds. These include complicated natural-product-like organic molecules, stable octahedral metal complexes, fullerenes, carboranes, polymetallic clusters, and even polymers. Thus the whole repertoire of organic, inorganic, and macromolecular chemistry can be applied to tackle the problem of target-specific enzyme inhibition.     

化学:人类生存和发展的基础——以诺贝尔化学奖为线索

截止2020年诺贝尔化学奖共颁发了112次,其见证了化学学科的发展历程、化学学科与人类生活密不可分的联系,以及化学学科发展的最前沿。以诺贝尔化学奖为主线,联系诺贝尔化学奖趣闻,讲解化学学科将是人类生存的基础,乃至对人类社会和生存发展做出的重要贡献,可以使大家认识到化学学科的重要性,并且更加了解如何进行化学研究,促进化学学科的长足发展。