| 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. |
- Eriksson, Ludvig, et al.
(författare)
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Feasibility of palladium catalysed isotopic exchange between [125I]iodide and 2-iodo-para-carborane
- 2003
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 46:7, s. 623-631
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Tidskriftsartikel (refereegranskat)abstract
- Many ortho-/meta-/para-closo-carborane derivatives have been proposed for boron neutron capture therapy. However, it is difficult to follow their pharmacokinetics in patients, which creates a risk of suboptimal treatment. Adding a radioactive label to closo-carboranes may simplify pharmacokinetic studies. This paper reports on a study of the feasibility of palladium-catalyzed isotopic exchange of iodinated closo-carborane with radioisotopes of iodine. 2-iodo-para-carborane was selected as a model compound. It was shown that such isotopic exchange is possible and provides a high yield (83±4.2%) after 40 min of reaction time. The reaction conditions were optimized, and it was demonstrated that the presence of tetra n-butylammonium hydrogensulfate is important in order to stabilize the catalyst and to give reproducibility of the labeling.
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| 3. |
- Ghirmai, Senait, et al.
(författare)
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Synthesis and Radioiodination of 7-(3´-Ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), (ANC)
- 2004
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 47:9, s. 557-569
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Tidskriftsartikel (refereegranskat)abstract
- Derivatives of nido-carborate have potential use in tumour targeting as hydrophilic boron-rich compounds for boron neutron capture therapy (BNCT) and as pendant groups for attachment of radiohalogens to tumour-seeking molecules. For this purpose, functionalized derivatives of nido-carborates that can be conjugated to biomolecules should be synthesized and evaluated. In this study, racemic 1, 7-(3′-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1) (acronym ANC) was obtained by degradation of the corresponding aminopropyl-o-carborane, which was synthesized in three steps from 1-tert-butyldimethylsilyl-2-(3-bromopropyl)-o-carborane, with sodium hydroxide in absolute ethanol. The racemate 1 was radioiodinated (125I) using the Chloramine-T method. Radio-TLC results showed that radiolabelling with 125I was achieved in a yield greater than 95%.
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| 4. |
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| 5. |
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| 6. |
- Ghirmai, Senait, et al.
(författare)
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Synthesis and radioiodination of some daunorubicin and doxorubicin derivatives
- 2005
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Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 340:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Daunorubicin and doxorubicin are efficient agents for cancer treatment. Their clinical efficacy is, however, hampered by their indiscriminant toxicity. This problem may be circumvented by encapsulating the drugs in liposomes and selectively targeting the tumor cells using tumor targeting agents. Furthermore, the antitumor effect could be enhanced by attaching the Auger electron emitter, 125I, to daunorubicin an ddoxorubicin derivatives. In this context a number of ester, amide, and amine derivatives of daunorubicin an ddoxorubicin were synthesized. Benzoic acid ester derivatives of daunorubicin were synthesized by nucleophilic esterification of the 14-bromodaunorubicin with the potassium salt of the corresponding benzoic acid, resulting in good yields. Nicotinic acids and benzoic acids, activated with a succinimidyl group, were coupled to the amino group of daunorubicien to give the corresponding amide derivatives. Amine derivatives were obtained by the reductive amination of aromatic aldehydes with daunorubicin hydrochloride. The stannylated ester and amide derivatives were uses as precursors for radioiodination. Radiolabeling with 125I was performed using chloroamine-T as an oxidant. The optimized labeling resulted in high radiolabeling yields (85-95%) of the radioiodinated daunorubicin and doxorubicin derivatives. Radioiodination of the amines was conducted at the ortho position of the activated phenyl rings providing moderate radiochemical yields (55-75%).
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| 7. |
- Ghirmai, Senait, 1974-
(författare)
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Synthesis of Organic Compounds for Nuclide Therapy : Derivatives of Carboranes, 9-Aminoacridine and Anthracyclines
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising. The thesis can be divided into three parts: i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield. ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam. iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented. The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.
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