| 1. |
- Bruskin, Alexander, et al.
(författare)
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Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-bromo-decahydro-closo-dodecaborate (Bromo-DABI)
- 2004
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 31:2, s. 205-11
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Tidskriftsartikel (refereegranskat)abstract
- The use of charged linkers in attaching radiohalogens to tumor-seeking biomolecules may improve intracellular retention of the radioactive label after internalization and degradation of targeting proteins. Derivatives of polyhedral boron clusters, such as closo-dodecaborate (2-) anion, might be possible charged linkers. In this study, a bifunctional derivative of closo-dodecaborate, (4-isothiocyanatobenzyl-ammonio)-undecahydro-closo-dodecaborate (DABI) was labeled with positron-emitting nuclide (76)Br (T 1/2 = 16.2 h) and coupled to anti-HER2/neu humanized antibody Trastuzumab. The overall labeling yield at optimized conditions was 80.7 +/- 0.6%. The label was proven to be stable in vitro in physiological and a set of denaturing conditions. The labeled antibody retained its capacity to bind to HER-2/neu antigen expressing cells. The results of the study demonstrated feasibility for using derivatives of closo-dodecaborate in indirect labeling of antibodies for radioimmunoPET.
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| 2. |
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| 3. |
- Orlova, Anna, et al.
(författare)
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Radio-iodination of monoclonal antibody using potassium [125I]-(4-isothiocyanatobenzylammonio)-iodo-decahydro-closo-dodecaborate (iodo-DABI)
- 2006
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:2A, s. 1217-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Negatively-charged polyhedral boron clusters can be easily halogenated with highly stable boron-halogen bonds and are promising in radionuclide diagnostics and cancer therapy. MATERIALS AND METHODS: The radio-iodination conditions for the closo-dodecaborate anion and for the conjugation of its labeled isothiocyanatobenzylammonio derivative to the monoclonal antibody (mAb) were optimized. RESULTS: The labeling yield was about 90% and the overall conjugation yield was 55-60%. The in vitro stability of the radio-iodinated mAb was good under physiological and non-physiological conditions. The immunoreactivity of the labeled mAb (SK-BR-3 cells) was retained in the one-pot two-step labeling. CONCLUSION: Negatively-charged polyhedral boron clusters can be used for indirect radio-iodination of mAbs.
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| 4. |
- Persson, Mikael, et al.
(författare)
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In vitro evaluation of two polyhedral boron anion derivatives as linkers for attachment of radioiodine to the anti-HER2 monoclonal antibody trastuzumab
- 2007
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 585-596
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Tidskriftsartikel (refereegranskat)abstract
- Improving intracellular retention is important for the use of radiohalogens in radionuclide therapy usinginternalizing antibodies. Two putative linkers for residualization of radioiodine labels, 7-(4-isothiocyanato-phenyl)undecahydro-7,8-dicarba-nido-undecaborate(1Ϫ) ion (NBI) and (4-isothiocyanato-benzylammo-nio)undecahydro-closo-dodecaborate(1Ϫ) (DABI), were analyzed. The anti-HER-2 antibody, trastuzumab,was labeled with iodine-125 using NBI and DABI linkers, and, for comparison, with the para-[125I]iodoben-zoate (PIB), and Chloramine-T (CAT) methods. The different labels were tested for residualizing prop-erties using the HER-2 overexpressing SKBR-3 cells. The cellular radioactivity retention showed thatDABI provided a 55% better retention than CAT and was 42% better than PIB after 20 hours. NBI didnot improve retention. Accumulation tests up to 21 hours showed that the HER-2-specific accumulationof radioactivity delivered with DABI was, on average, 33% higher than with the use of PIB. These DABI-dependent improvements could, with high probability, be attributed to the good residualizing propertiesof DABI. The affinity of DABI-labeled trastuzumab to SKBR-3 cells was not better than the affinity of thePIB labeled (3.2 Ϯ 1.9 nM and 0.77 Ϯ 0.39 nM, respectively). In conclusion, the use of the DABI linkerimproved intracellular retention in vitro in comparison with the other labeling methods.
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| 5. |
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| 6. |
- Sivaev, Igor B., et al.
(författare)
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The synthesis of functional derivatives of the [1-CB9H10]-anion by Brellochs reaction
- 2005
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Ingår i: Journal of Organo metallic Chemistry. ; :690, s. 2790-2795
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Tidskriftsartikel (refereegranskat)abstract
- Reactions of decarborane with various aldehydes in alkaline media were studied. The reactions with HCOH and 2-MeOC6H4-CHO give the corresponding arachno-carboranes [6-R-arachno-CB9H13]-(R=H, C6H4-2-OMe), whereas the reactions with C6H5CHO, 4-BrC6H4CHO, 4-MeCONHC6H4CHO and 2-SC4H3CHO result in the nido-carboranes [6-R-nido-CB9H11]-(R=C6H5, C6H4-4Br, C6H4-4-NHCOMe, 2-SC4H3). Both the arachno- and nido-carboranes can be easily oxidized with elemental iodine in an alkaline aqueous solution giving the corresponding closo-derivatives [2-R-closo-2-CB9H9]-. These closo-2isomers, under heating in solution, undergo rearrangement to more thermodynamically favorable closo-1-isomers [1-R-closo-1-CB9H9]-. The structure of (Bu4N)[1-(4-BrC6H4)-1-CB9H9] was determined using single crystal X-ray diffraction.
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| 7. |
- Sivaev, Igor
(författare)
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Synthesis of functional derivatives of [B12H12]2- anion for boron neutron capture therapy, radiodiagnostics and radioimmunotherapy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Functional derivatives of dodecahydro-closo-dodecaborate anion [B12H12]2- are potential candidates for medical application in boron neutron capture therapy for cancer and as linkers for the introduction of radiohalogen label into biomolecules for radioimmunodiagnostics and radioimmunotherapy.In this study, new approaches for the synthesis of functional derivatives of the closo-dodecaborate anion were developed and a series of novel functional derivatives were prepared. The alkylation of [B12H11]2- gave the corresponding alkoxy derivatives [B12H11]2- which can be used for synthesis of functional derivatives by functional group interconversion reactions.A series of derivatives containing functional groups attached to the boron cage through long aliphatic chains [B12H11O(CH2)4X]2- (X = OH, NH2, COOH,CH(NH2)COOH) were prepared by ring-opening reactions of the tetramethylene oxonium derivative [B12H11O(CH2)4]- with different nucleophiles.The reaction of [B12H11NH3]- with aldehydes followed by reduction of the Schiff bases formed was used for synthesis of a series of derivatives containing functional groups attached to the boron cage through an aromatic ring [B12H11NH2CH2C6H4-4-X]- (X = NH2, COOH, NCS). The structures of (Bu4N)[B12H11NH=CHC6H4-4-NMe2] and (Bu4N)[B12H11NH=CHC6H4-2-OMe] were determined by single crystal X-ray diffraction.A new method for the synthesis of the carbonyl derivative [B12H11CO]-, a potential synthon for the synthesis of new derivatives with boron-carbon bonds, was elaborated.A new approach to synthesis of water-soluble carboranes using the closo-dodecaborate cage as a hydrophilic substituent was proposed. The double-cage molecules synthesized [ o-, m-, and p-CB10H10(CH2)4OB12H11]2- can be used for the attachment to biomolecules via the carbon atom of the carborane cage using earlier developed methods.
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| 8. |
- Tolmachev, Vladimir, et al.
(författare)
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Closo-dodecaborate(2-) as a linker for iodination of macromolecules : Aspects on conjugation chemistry and biodistribution
- 1999
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 10:3, s. 338-45
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Tidskriftsartikel (refereegranskat)abstract
- Boron-containing compounds like closo-dodecaborate(2-) are in theory suitable for radioactive labeling with halogens. The boron-halogen bond is stronger than carbon-halogen bond and is not likely to be recognized by deiodinating enzymes in vivo. Peptides and proteins may be conjugated with various closo-dodecaborate(2-)-containing ligands, and thereafter, the conjugate can be iodinated. Since closo-dodecaborate(2-) is more avidly iodinated than tyrosine in moderately acidic media, such conjugates may be directly labeled on the boron part with radioisotopes of iodine using the standard Chloramine-T procedure. Mercapto-undecahydro-closo-dodecaborate(2-) (BSH) was reacted with the double bond of allyldextran to form a boronated dextran compound of the molecular size of about 70 kDa. This compound, in the text denoted as Dx-BS, and cesium dodecahydro-closo-dodecaborate(2-) were labeled using iodine-125. The two compounds were administered to rats in order to study their in vivo stability. The results indicate that iodinated Dx-BS is stable for about 20 h in vivo. The degradation rate, as indicated by thyroid uptake, was found low. [125I]Iodo-closo-dodecaborate(2-), which is a possible degradation product of [125I]Dx-BS-I, was rapidly excreted in urine without significant accumulation in any organ.
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| 10. |
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