Structure of the barium salt of a Cu2+ complex with a tetraaza macrocyclic tetraacetate

Riesen, Andreas; Zehnder, Margareta; Kaden, Thomas A.

doi:10.1107/s0108270188006365

Cited by 24 publications

(22 citation statements)

References 1 publication

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“…Some X-ray crystal structures confirm this point, such as in [Cu(ac 3 py14)] - [18] and in [Co(ac 3 py14)] [18], in which the six-coordination is completed with two oxygen atoms from contiguous acetate arms. This is also the case of [M(dota)] 2-and [M(teta)] 2-(M = Cu 2+ or Ni 2+ ) [19][20][21][22] where the metal centers adopt an octahedral geometry with the four nitrogen atoms of the macrocycle forming the equatorial plane and two oxygen atoms from opposed acetate arms occupying the axial positions, leaving the two other arms free and pointing away from the coordination sphere. In contrast, lanthanide ions generally form complexes with higher coordination numbers, such as in [Eu(dota)(H 2 O)] - [23] and [Gd(dota)(H 2 O)] - [24] or [Tb(teta)] - [25] and [Eu(teta)] - [26], for which single-crystal X-ray structures were reported.…”

Section: Discussionmentioning

confidence: 99%

Lanthanide complexes of macrocyclic derivatives useful for medical applications

Delgado

Costa

Guerra

et al. 2005

Pure and Applied Chemistry

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Abstract:The protonation constants of two series of tetraazamacrocyclic ligands with acetate and methylphosphonate pendant arms, as well as their stability constants with Cu 2+ , La 3+ , Sm 3+ , and Ho 3+ , were determined. All the values were determined in aqueous solution at 298.0 K and 0.10 mol dm -3 in N(CH 3 ) 4 NO 3 . In the first series, the effect of both types of pendant arms was observed by appending them in the same macrocyclic backbone, a 14-membered tetraazamacrocycle containing pyridine (ac 3 py14, p 2 py14, and p 3 py14). In the second series, two effects were taken into account, the increase of the cavity size of the macrocycle, from 12-to 14-membered, and the appending of acetate (dota, trita, and teta) or methylphosphonate (dotp, tritp, and tetp) arms. The ligands containing methylphosphonate arms have higher thermodynamic stability compared to the corresponding ones with acetate arms, especially in the series of compounds containing pyridine, even upon correction of the different basicity values of the ligands. On the other hand, the ligands with smaller macrocyclic cavity size, namely, dota and dotp, exhibit the largest values of stability constants. In contrast, ac 3 py14 presents low stability constants with lanthanides. An interpretation of these features based on the known adopted arrangement of dota and teta when free or coordinated with lanthanides is evaluated.

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Section: Discussionmentioning

confidence: 99%

Lanthanide complexes of macrocyclic derivatives useful for medical applications

Delgado

Costa

Guerra

et al. 2005

Pure and Applied Chemistry

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“…These systems have been thoroughly investigated, and in vitro and in vivo testing have shown them to be superior to acyclic chelating agents for 64 Cu 6. This enhanced stability is most likely due to the greater geometrical constraint incorporated into the macrocyclic ligand that enhances the kinetic inertness and thermodynamic stability of their 64 Cu complexes 9,10. Two of the most important chelators studied were DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid).…”

Section: Chelators Based On Cyclam and Cyclen Backbonesmentioning

confidence: 99%

Molecular Imaging of Cancer with Copper-64 Radiopharmaceuticals and Positron Emission Tomography (PET)

Shokeen¹,

2009

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Molecular imaging has evolved over the past several years into an important tool for diagnosing, understanding, and monitoring disease. Molecular imaging has distinguished itself as an interdisciplinary field, with contributions from chemistry, biology, physics, and medicine. The cross-disciplinary impetus has led to significant achievements, such as the development of more sensitive imaging instruments and robust, safer radiopharmaceuticals, thereby providing more choices to fit personalized medical needs. Molecular imaging is making steadfast progress in the field of cancer research among others. Cancer is a challenging disease, characterized by heterogeneity, uncontrolled cell division, and the ability of cancer cells to invade other tissues. Researchers are addressing these challenges by aggressively identifying and studying key cancer-specific biomarkers such as growth factor receptors, protein kinases, cell adhesion molecules, and proteases, as well as cancer-related biological processes such as hypoxia, apoptosis, and angiogenesis. Positron emission tomography (PET) is widely used by clinicians in the United States as a diagnostic molecular imaging tool. Small-animal PET systems that can image rodents and generate reconstructed images in a noninvasive manner (with a resolution as low as 1 mm) have been developed and are used frequently, facilitating radiopharmaceutical development and drug discovery. Currently, [18F]-labeled 2-fluorodeoxyglucose (FDG) is the only PET radiotracer used for routine clinical evaluation (primarily for oncological imaging). There is now increasing interest in nontraditional positron-emitting radionuclides, particularly those of the transition metals, for imaging with PET because of increased production and availability. Copper-based radionuclides are currently being extensively evaluated because they offer a varying range of half-lives and positron energies. For example, the half-life (12.7 h) and decay properties (β+, 0.653 MeV, 17.8%; β−, 0.579 MeV, 38.4 %; the remainder is electron capture) of 64Cu make it an ideal radioisotope for PET imaging and radiotherapy. In addition, the well-established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to antibodies, proteins, peptides, and other biologically relevant molecules. New chelators with greater in vivo stability, such as the cross-bridged (CB) versions of tetraazamacrocyclic 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA), are now available. Finally, one of the major aspects of successful imaging is the identification and characterization of a relevant disease biomarker at the cellular and subcellular level and the ensuing development of a highly specific targeting moiety. In this Account, we discuss specific examples of PET imaging with new and improved 64Cu-based radiopharmaceuticals, highlighting the study of some of the key cancer biomarkers, such as epidermal growth-factor receptor (EGFR), somatostatin receptors (SSRs), a...

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“…Cu(II)-CB-TE2A complex has an octahedral complex with 2 axial nitrogens, 2 equatorial nitrogens, and carboxylate groups at the remaining 2 cis-equatorial positions as particular features (44). Cu(II)-TETA forms a distorted octahedron with 2 weakly coordinated axial carboxylates, whereas the 4 nitrogens of the tetraazamacrocycle are at equatorial positions (45). The 2 complexes have different overall charges.…”

Section: Discussionmentioning

confidence: 99%

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

et al. 2019

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Prostate-specific membrane antigen (PSMA)-binding tracers have been shown to be promising agents for the specific targeting of prostate tumors. On labeling with the short-lived isotopes 18 F and 68 Ga, excellent molecular imaging performance is achieved. This potential could be further exploited using long-lived isotopes. Because of the favorable half-life of 64 Cu, tracers labeled with this PET nuclide could solve logistic problems. Moreover, this isotope provides a theranostic pair with the therapeutic copper isotope 67 Cu. Hence, 9 novel tracers that combine dedicated copper chelators with the PSMA-specific urea-based binding motif were developed. Methods: The precursors were obtained by solid-phase synthesis. The purity and molecular weight of the PSMA ligands were confirmed by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The compounds were labeled with 64 Cu, with a radiolabeling yield of more than 99%. Competitive cell binding assays and internalization assays were performed with C4-2 cells, a subline of the PSMA-positive cell line LNCaP (human lymph node carcinoma of the prostate). In vitro serum stability, the stability of 64 Cu-CA003 in blood, and the in vivo fate of neat 64 Cuchloride or 64 Cu-CA003 were determined to prove whether the stability of the radiolabeled compounds is sufficient to ensure no significant loss of copper during the targeting process. For PET imaging and biodistribution studies, a C4-2 tumor-bearing mouse model was used. Results: The radiolabeled 64 Cu-PSMA ligands showed high serum stability. All PSMA ligands showed high inhibition potencies, with equilibrium inhibition constants in the low nanomolar range. 64 Cu-CA003 and 64 Cu-CA005 showed high internalization ratios (34.6% ± 2.8 and 18.6% ± 4.4, respectively). Both the in vitro serum stability determination and the in vivo characterization of the main radiolabeled compounds confirmed that, except for 64 Cu-PSMA-617, all compounds showed high serum stability within the observation period of 24 h. Small-animal PET imaging demonstrated high tumor uptake within 20 min. Organ distribution studies confirmed high specific uptake in the tumor, with 30.8 ± 12.6 percentage injected dose (%ID)/g at 1 h after injection. Rapid clearance from the kidneys was observed-a decrease from 67.0 ± 20.9 %ID/g at 1 h after injection to 7.5 ± 8.51 %ID/g at 24 h after injection (in the case of CA003). The performance of CA003, the compound with the best preclinical properties, was assessed in a first patient. In line with its preclinical data, PET imaging resulted in clear visualization of the cancer lesions, with high contrast. Conclusion: The 64 Culabeled PSMA ligands are promising agents to target PSMA and visualize PSMA-positive tumor lesions as shown in preclinical evaluation by small-animal PET studies, organ distribution, and a patient application. Most importantly, the images obtained at 20 h enabled delineation of unclear lesions, showing that the compounds fulfill the prerequisite for dosimetry in the co...

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Structure of the barium salt of a Cu2+ complex with a tetraaza macrocyclic tetraacetate

Cited by 24 publications

References 1 publication

Lanthanide complexes of macrocyclic derivatives useful for medical applications

Lanthanide complexes of macrocyclic derivatives useful for medical applications

Molecular Imaging of Cancer with Copper-64 Radiopharmaceuticals and Positron Emission Tomography (PET)

Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes

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