Coordination Chemistry and Ligand Design in the Development of Metal Based Radiopharmaceuticals

Boros, Eszter; Marquez, Bernadette V.; Ikotun, Oluwatayo F.; Lapi, Suzanne E.; Ferreira, Cara L.

doi:10.1002/9781118697191.ch3

Cited by 10 publications

(28 citation statements)

References 156 publications

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“…In order to establish the structure and redox chemistry of BMS181321, a 99 Tc standard, 99 TcO(PnAO-1-(2-nitroimidazole), was isolated and characterized. X-ray crystallographic analysis demonstrated 4 nitrogen atoms of PnAO coordinating with the Tc(V) centre, with the oxygen atom occupying the apical position resulting in a square pyramidal geometry.…”

Section: Technetium Nitroimidazole Complexesmentioning

confidence: 99%

“…TcCl(dioxime)3 to form complexes 23 to 27, and 99 Tccyclohexanedione dioxime (CDO) to afford compounds 28 and 29. While the preparation of most compounds proceeded in a straightforward manner, TcCl(DMG)3BPhEtNO2 (25) was formed from an unidentified intermediate only upon recrystallization from HC1-acidified DMF.…”

Section: Boronic Acid Adducts Of Technetium Dioximes (Bato)mentioning

confidence: 99%

“…Indium-111 decays via electron capture (EC) with gamma emissions having 173 keV (89%) and 247 keV (94%) energies, thus, making it a very useful clinical SPECT imaging agent [98][99]. Furthermore, the emission of Auger electrons offers potential for radiotherapeutic applications [100].…”

Section: Indium Nitroimidazole Complexesmentioning

confidence: 99%

“…In addition to octahedral complexes, it can also accommodate more donor groups to form 7-and 8-coordinate complexes. Polydentate ligands having carboxylate and amino functionalities are good chelating partners [99].…”

Section: +mentioning

confidence: 99%

“…Electrochemical studies revealed that the redox chemistry of the nitroimidazole moiety was maintained upon coordination to Tc, with a reversible reduction process at -1.48 V. Additionally, the cyclic voltammogram showed an irreversible reduction process at -1.99 V, which was assigned to the 99 TcPnAO core [50]. Biodistribution studies performed in mice implanted with KHT, SCC-VII and RIF-1 tumours provided T/M ratios of 3.94, 3.34 and 3.49; respectively, 6 h after intravenous injection [51].…”

mentioning

confidence: 95%

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Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Ricardo¹,

Kumar²,

Wiebe³

2015

J Diagn Imaging Ther

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Oxygen supply -demand imbalances can render proliferating cells acutely or chronically hypoxic. In cancer cells, hypoxia-induced pathophysiological changes give rise to genetic changes that lead to treatment-resistant, aggressive phenotypes. The reduced curability of hypoxic tumours by radiotherapy is one of consequent challenges, but their hypoxia also offers unique, exploitable properties. Nitroimidazoles, for example, capitalize on oxygen-sensitive reductive activation to achieve hypoxiaselective localization for theranostic consequence. The discovery of 2-nitroimidazole (azomycin) heralded the development of many drugs, including effective radiosensitizers of hypoxic cells. These electron-affinic, reductively bioactivated nitroheterocyclics undergo initial oxygen-reversible, enzymatic one-electron reductions that lead to the formation of molecular adducts that impair vital

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Section: Technetium Nitroimidazole Complexesmentioning

confidence: 99%

Section: Boronic Acid Adducts Of Technetium Dioximes (Bato)mentioning

confidence: 99%

Section: Indium Nitroimidazole Complexesmentioning

confidence: 99%

Section: +mentioning

confidence: 99%

mentioning

confidence: 95%

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Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Ricardo¹,

Kumar²,

Wiebe³

2015

J Diagn Imaging Ther

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Incorporation of Carboxylate Pendant Arms into 18‐Membered Macrocycles: Effects on [^nat/203Pb]Pb(II) Complexation

Harriswangler,

McNeil,

Brandariz

et al. 2024

Chemistry A European J

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We present a detailed investigation on the coordination chemistry of [nat/203Pb]Pb(II) with chelators H4PYTA and H4CHX‐PYTA. These chelators belong to the family of ligands derived from the 18‐membered macrocyclic backbone PYAN and present varying degrees of rigidity due to the presence of either ethyl or cyclohexyl spacers. A complete study of the stable Pb(II) complexes is carried out via NMR, X‐Ray crystallography, stability constant determination and computational studies. While these studies indicated that Pb(II) complexation is achieved, and the thermodynamic stability of the resulting complexes is very high, a certain degree of fluxionality does exist in both cases. Nevertheless, radiolabeling studies were carried out using SPECT (single photon emission computed tomography) compatible isotope lead‐203 (203Pb, t1/2 = 51.9 h), and while both chelators complex the radioisotope, the incorporation of carboxylate pendant arms appears to be detrimental towards the stability of the complexes when compared to the previously described amide analogues. Additionally, incorporation of a cyclohexyl spacer does not improve the kinetic inertness of the system.

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Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics

et al. 2021

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We show the synthesis of an in vivo stable mercury compound with functionality suitable for radiopharmaceuticals. The designed cyclic bisarylmercury was based on the water tolerance of organomercurials, higher bond dissociation energy of HgÀ Ph to HgÀ S, and the experimental evidence that acyclic structures suffer significant cleavage of one of the HgÀ R bonds. The bispidine motif was chosen for its in vivo stability, chemical accessibility, and functionalization properties. Radionuclide production results in 197(m) HgCl 2 (aq), so the desired mercury compound was formed via a water-tolerant organotin transmetallation. The Hg-bispidine compound showed high chemical stability in tests with an excess of sulfur-containing competitors and high in vivo stability, without any observable protein interaction by human serum assay, and good organ clearance demonstrated by biodistribution and SPECT studies in rats. In particular, no retention in the kidneys was observed, typical of unstable mercury compounds. The nat Hg analogue allowed full characterization by NMR and HRMS.

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Coordination Chemistry and Ligand Design in the Development of Metal Based Radiopharmaceuticals

Cited by 10 publications

References 156 publications

Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Incorporation of Carboxylate Pendant Arms into 18‐Membered Macrocycles: Effects on [^nat/203Pb]Pb(II) Complexation

Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics

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Coordination Chemistry and Ligand Design in the Development of Metal Based Radiopharmaceuticals

Cited by 10 publications

References 156 publications

Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Incorporation of Carboxylate Pendant Arms into 18‐Membered Macrocycles: Effects on [nat/203Pb]Pb(II) Complexation

Radiolabelled Cyclic Bisarylmercury: High Chemical and in vivo Stability for Theranostics

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Resources

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Incorporation of Carboxylate Pendant Arms into 18‐Membered Macrocycles: Effects on [^nat/203Pb]Pb(II) Complexation