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| [PMID]: | 25684650 |
| [Au] Autor: | Wilson JJ; Ferrier M; Radchenko V; Maassen JR; Engle JW; Batista ER; Martin RL; Nortier FM; Fassbender ME; John KD; Birnbaum ER |
| [Ad] Endereço: | Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, NM, 87545, USA. Electronic address: jjwilson@lanl.gov. |
| [Ti] Título: | Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes. |
| [So] Source: | Nucl Med Biol;42(5):428-38, 2015 May. | | [Is] ISSN: | 1872-9614 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | INTRODUCTION: The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope (213)Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi(3+), however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. METHODS: The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), were prepared by a previously reported method and investigated here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[(R)-2-amino-3-(p-isothiocyanato-phenyl)propyl]-trans-(S,S)- cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, (207)Bi (t(1/2)=32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi(3+) and the generator parent ion Ac(3+). RESULTS: In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi(3+) in the presence of the parent isotope Ac(3+). Among the four tested, L(py) was found to exhibit optimal Bi(3+)-binding kinetics and complex stability. L(py) complexes Bi(3+) more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi(3+) over Ac(3+). CONCLUSION: Taken together, these data implicate L(py) as a valuable chelating agent for the delivery of (213)Bi. Its selectivity for Bi(3+) and rapid and stable labeling properties warrant further investigation and biological studies. |
| [Mh] Termos MeSH primário: |
Bismuto/química
Bismuto/uso terapêutico
Quelantes/química
Compostos Macrocíclicos/química
Nitrogênio/química
Radioisótopos
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| [Mh] Termos MeSH secundário: |
Actínio/química
Partículas alfa/uso terapêutico
Ligação Competitiva
Ácido Edético/química
Marcação por Isótopo
Cinética
Ligantes
Teoria Quântica
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Chelating Agents); 0 (Ligands); 0 (Macrocyclic Compounds); 0 (Radioisotopes); 9G34HU7RV0 (Edetic Acid); N762921K75 (Nitrogen); NIK1K0956U (Actinium); U015TT5I8H (Bismuth) |
| [Em] Mês de entrada: | 1603 |
| [Cu] Atualização por classe: | 150406 |
[Lr] Data última revisão:
| 150406 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 150217 |
| [St] Status: | MEDLINE |
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