Chemical Reviews is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 “Green” Atom Transfer Radical Polymerization: From Process Design to Preparation of Well-Defined Environmentally Friendly Polymeric Materials Nicolay V. Tsarevsky, and Krzysztof Matyjaszewski Chem. Rev., 2007, 107 (6), 2270-2299• DOI: 10.1021/cr050947p • Publication Date (Web): 27 May 2007 Downloaded from http://pubs.acs.org on April 2, 2009

"Green" atom transfer radical polymerization: from process design to preparation of well-defined environmentally friendly polymeric materials.

Molecular imaging is the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Molecular imaging agents are probes used to visualize, characterize and measure biological processes in living systems. These two definitions were put forth by the Sociey of Nuclear Medicine (SNM) in 2007 as a way to capture the interdisciplinary nature of this relatively new field. The emergence of molecular imaging as a scientific discipline is a result of advances in chemistry, biology, physics and engineering, and the application of imaging probes and technologies has reshaped the philosophy of drug discovery in the pharmaceutical sciences by providing more cost effective ways to evaluate the efficacy of a drug candidate and allowing pharmaceutical companies to reduce the time it takes to introduce new therapeutics to the marketplace. Finally the impact of molecular imaging on clinical medicine has been extensive since it allows a physician to diagnose a patient’s illness, prescribe treatment and monitor the efficacy of that treatment non-invasively.

Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) were the first molecular imaging modalities used clinically. SPECT requires the use of a contrast agent labeled with a gamma emitting radionuclide, which should have an ideal gamma energy of 100-250 keV. These gamma rays are recorded by the detectors of a dedicated gamma camera or SPECT instrument and after signal processing can be converted into an image indentifying the localization of the radiotracer. PET requires the injected radiopharmaceutical to be labeled with a positron emitting radionuclide. As the radionuclide decays it ejects a positron from its nucleus which travels a short distance before being annihilated with an electron to release two 511 keV gamma rays 180° apart that are detected by the PET scanner (Figure 1). After sufficient acquisition time the data are reconstructed using computer based algorithms to yield images of the radiotracer’s location within the organism. When compared to SPECT, PET has greater advantages with respect to sensitivity and resolution and has been gaining in clinical popularity, with the number of PET-based studies expected to reach 3.2 million by 2010.1 While SPECT and PET technology has been around for decades, its use remained limited because of the limited availability of relevant isotopes which had to be produced in nuclear reactors or particle accelerators. However, the introduction of the small biomedical cyclotron, the self-contained radionuclide generator and the dedicated small animal or clinical SPECT and PET scanners to hospitals and research facilities has increased the demand for SPECT and PET isotopes.



Figure 1

Cartoon depicting the fundamental principle of Positron Emission Tomography (PET). As the targeting group interacts with the cell surface receptor, the positron emitting radio-metal decays by ejecting β+ particles from its nucleus. After traveling ...



Traditional PET isotopes such as 18F, 15O, 13N and 11C have been developed for incorporation into small molecules, but due to their often lengthy radio-syntheses, short half-lives and rapid clearance, only early time points were available for imaging, leaving the investigation of biological processes, which occur over the duration of hours or days, difficult to explore. With the continuing development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles, which demonstrate a range of biological half-lives, a need arose to produce new radionuclides with half-lives complementary with their biological properties. As a result, the production and radiochemistry of radiometals such as Zr, Y, In, Ga and Cu have been investigated as radionuclide labels for biomolecules since they have the potential to combine their favorable decay characteristics with the biological characteristics of the targeting molecule to become a useful radiopharmaceutical (Tables ​(Tables11 and ​and22).2



Table 1

Gamma- and Beta-Emitting Radiometals





Table 2

Positron-Emitting Radiometals



The number of papers published describing the production or use of these radiometals continues to expand rapidly, and in recognition of this fact, the authors have attempted to present a comprehensive review of this literature as it relates to the production, ligand development and radiopharmaceutical applications of radiometals (excluding 99mTc) since 1999. While numerous reviews have appeared describing certain aspects of the production, coordination chemistry or application of these radiometals,2-18 very few exhaustive reviews have been published.10,12 Additionally, this review has been written to be used as an individual resource or as a companion resource to the review written by Anderson and Welch in 1999.12 Together, they provide a literature survey spanning 50 years of scientific discovery. To accomplish this goal, this review has been organized into three sections: the first section discusses the coordination chemistry of the metal ions Zr, Y, In, Ga and Cu and their chelators in the context of radiopharmaceutical development; the second section describes the methods used to produce Zr, Y, In, Ga and Cu radioisotopes; and the final section describes the application of these radiometals in diagnostic imaging and radiotherapy.

/pdf/coordinating-radiometals-of-copper-gallium-indium-yttrium-3clup681fj.pdf

Coordinating Radiometals of Copper, Gallium, Indium, Yttrium and Zirconium for PET and SPECT Imaging of Disease

Radiometals comprise many useful radioactive isotopes of various metallic elements When properly harnessed, these have valuable emission properties that can be used for diagnostic imaging techniques, such as single photon emission computed tomography (SPECT, eg67Ga, 99mTc, 111In, 177Lu) and positron emission tomography (PET, eg68Ga, 64Cu, 44Sc, 86Y, 89Zr), as well as therapeutic applications (eg47Sc, 114mIn, 177Lu, 90Y, 212/213Bi, 212Pb, 225Ac, 186/188Re) A fundamental critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand system that binds the radiometal ion in a tight stable coordination complex so that it can be properly directed to a desirable molecular target in vivo This article is a guide for selecting the optimal match between chelator and radiometal for use in these systems The article briefly introduces a selection of relevant and high impact radiometals, and their potential utility to the fields of radiochemistry, nuclear medicine, and molecular imaging A description of radiometal-based radiopharmaceuticals is provided, and several key design considerations are discussed The experimental methods by which chelators are assessed for their suitability with a variety of radiometal ions is explained, and a large selection of the most common and most promising chelators are evaluated and discussed for their potential use with a variety of radiometals Comprehensive tables have been assembled to provide a convenient and accessible overview of the field of radiometal chelating agents

Matching chelators to radiometals for radiopharmaceuticals.

Equilibrium constants in Cu-based atom transfer radical polymerization (ATRP) were determined for a wide range of ligands and initiators in acetonitrile at 22 °C. The ATRP equilibrium constants obtained vary over 7 orders of magnitude and strongly depend on the ligand and initiator structures. The activities of the CuI/ligand complexes are highest for tetradentate ligands, lower for tridentate ligands, and lowest for bidentate ligands. Complexes with tripodal and bridged ligands (Me6TREN and bridged cyclam) tend to be more active than those with the corresponding linear ligands. The equilibrium constants are largest for tertiary alkyl halides and smallest for primary alkyl halides. The activities of alkyl bromides are several times larger than those of the analogous alkyl chlorides. The equilibrium constants are largest for the nitrile derivatives, followed by those for the benzyl derivatives and the corresponding esters. Other equilibrium constants that are not readily measurable were extrapolated from t...

Understanding atom transfer radical polymerization: effect of ligand and initiator structures on the equilibrium constants.

Thlaspi goesingense is able to hyperaccumulate extremely high concentrations of Ni when grown in ultramafic soils. Recently it has been shown that rhizosphere bacteria may increase the heavy metal concentrations in hyperaccumulator plants significantly, whereas the role of endophytes has not been investigated yet. In this study the rhizosphere and shoot-associated (endophytic) bacteria colonizing T. goesingense were characterized in detail by using both cultivation and cultivation-independent techniques. Bacteria were identified by 16S rRNA sequence analysis, and isolates were further characterized regarding characteristics that may be relevant for a beneficial plant-microbe interaction—Ni tolerance, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase and siderophore production. In the rhizosphere a high percentage of bacteria belonging to the Holophaga/Acidobacterium division and α-Proteobacteria were found. In addition, high-G+C gram-positive bacteria, Verrucomicrobia, and microbes of the Cytophaga/Flexibacter/Bacteroides division colonized the rhizosphere. The community structure of shoot-associated bacteria was highly different. The majority of clones affiliated with the Proteobacteria, but also bacteria belonging to the Cytophaga/Flexibacter/Bacteroides division, the Holophaga/Acidobacterium division, and the low-G+C gram-positive bacteria, were frequently found. A high number of highly related Sphingomonas 16S rRNA gene sequences were detected, which were also obtained by the cultivation of endophytes. Rhizosphere isolates belonged mainly to the genera Methylobacterium, Rhodococcus, and Okibacterium, whereas the majority of endophytes showed high levels of similarity to Methylobacterium mesophilicum. Additionally, Sphingomonas spp. were abundant. Isolates were resistant to Ni concentrations between 5 and 12 mM; however, endophytes generally tolerated higher Ni levels than rhizosphere bacteria. Almost all bacteria were able to produce siderophores. Various strains, particularly endophytes, were able to grow on ACC as the sole nitrogen source.

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Bacterial Communities Associated with Flowering Plants of the Ni Hyperaccumulator Thlaspi goesingense

Macrocyclic chelators and their metal complexes have widespread applications in the biomedical sciences, including radiopharmaceutical chemistry. The use of copper radionuclides in radiopharmaceuticals is increasing. Macrocyclic chelators have been found to have enhanced in vivo stability over acyclic chelators such as ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). The currently used chelators of choice for labeling copper radionuclides to biological molecules are analogues of TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid); however, recent reports have demonstrated evidence of in vivo instability of the radio-Cu(II)−TETA complexes. A new class of structurally reinforced macrocycles, the “cross-bridged” cyclam derivatives, form highly stable complexes with Cu(II) that are resistant to dissociation in strong acid. Here, we evaluate a series of 64Cu(II) cross-bridged macrocyclic complexes for biological stability and in vivo behavior. The ligands eva...

Radiolabeling and In Vivo Behavior of Copper-64-Labeled Cross-Bridged Cyclam Ligands

Tris(2-mercaptobenzyl)amine, S3N, and tris(2-hydroxybenzyl)amine, O3N, were investigated with In3+ and Ga3+ in solution and in the solid state to help interpret the contrasting in vivo behavior of ...

The Gallium(III) and Indium(III) Complexes of Tris(2-mercaptobenzyl)amine and Tris(2-hydroxybenzyl)amine

Metal Ion Recognition in Ligands with Negatively Charged Oxygen Donor Groups. Complexation of Fe(III), Ga(III), In(III), Al(III), and Other Highly Charged Metal Ions.

N,N‘-ethylenedi-l-cysteine (EC) and its indium(III) and gallium(III) complexes have been synthesized and characterized. The crystal structures of the ligand and the complexes have been determined by single-crystal X-ray diffraction. EC·2HBr·2H2O (C8H22Br2N2O6S2) crystallizes in the orthorhombic space group P21212 with a = 12.776(3) A, b = 13.735(2) A, c = 5.1340 (10) A, Z = 2, and V = 900.9(3) A3. The complexes Na[M(III)EC]·2H2O (C8H16MN2O6S2Na) are isostructural for M = In and Ga, crystallizing in the tetragonal space group P42212 with the following lattice constants for In, (Ga):  a = 10.068(2) A, (9.802(2) A), b = 10.068(2) A, (9.802(2) A), c = 14.932(2) A, (15.170(11) A), Z = 4 (4), and V = 1513.6(5) A3, (1457.5(11) A3). In both metal complexes, the metal atoms (In and Ga) are coordinated by six donor atoms (N2S2O2) in distorted octahedral coordination geometries in which two sulfur atoms and two nitrogen atoms occupy the equatorial positions, and the axial positions are occupied by two oxygen atoms o...

Arthur E. Martell

Papers

Radiolabeling and In Vivo Behavior of Copper-64-Labeled Cross-Bridged Cyclam Ligands

The Gallium(III) and Indium(III) Complexes of Tris(2-mercaptobenzyl)amine and Tris(2-hydroxybenzyl)amine

Metal Ion Recognition in Ligands with Negatively Charged Oxygen Donor Groups. Complexation of Fe(III), Ga(III), In(III), Al(III), and Other Highly Charged Metal Ions.

N,N'-Ethylenedi-L-cysteine (EC) and Its Metal Complexes: Synthesis, Characterization, Crystal Structures, and Equilibrium Constants.

New multidentate ligands. XVII. Chelating tendencies of N-(o-hydroxybenzyl)iminodiacetic acid (H3L)