Rapid radiohalogenations of small molecules—II. Radiobromination of tyrosine, uracil and cytosine

Hadi, U.A.M.; Malcolme-Lawes, David J.; Oldham, G.

doi:10.1016/0020-708x(79)90114-5

Cited by 15 publications

(6 citation statements)

References 9 publications

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“…Another bromine radionuclide, bromine-75 has a half-life of 97 min, which is similar to that of fluorine-18, but it has a positron emission of 1. 74 MeV in 75% abundance. While bromine-75 may be produced at higher specific activities than fluorine-18, unless there are significant difficulties in labeling of proteins with fluorine-18, it is not likely to be used in its place.…”

Section: Radionuclides Of Halogensmentioning

confidence: 97%

“…Since the reactions are conducted in a separate vessel from the protein, stronger oxidizing reagents can be used without affecting the protein. Many examples of chloramine-T oxidations of halides for radiohalogenations of small molecules have been reported (74)(75)(76). The reactions have generally been conducted in aqueous solutions, but the salt is also soluble in some aprotic solvents such as trifluoroacetic anhydride (77).…”

Section: Radiohalogen Labelingmentioning

confidence: 99%

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Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

Ds¹

1992

Bioconjugate Chem.

224

176

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Direct labeling of proteins with radionuclides of iodine will continue to be the method of choice to answer questions addressed in many future studies. However, it seems likely that a increasing number of applications of radiohalogenated proteins will require, or benefit from, conjugate labeling. While many radiohalogen conjugates have been studied, a large proportion of them have only undergone preliminary studies to date, leaving a question of their overall utility. Phenolic conjugates give good radioiodination labeling yields, but mixtures of radiohalogenated products and problems with in vivo stability can be expected. This fact, along with the fact that phenolic compounds do not have a general application to radiohalogens, makes them less attractive than other alternatives. Radiohalogen labeling through the use of organometallic intermediates has proven to be facile, resulting in high yields of high specific activity labeled small-molecule conjugates. Although the choice of which organometallic intermediate to use may depend somewhat on the radionuclide employed, arylstannanes appear to have the most general applicability. Fluorine-18 labeling of small-molecule conjugates has been best accomplished by ipso aromatic nucleophilic substitution (exchange) reactions. Radiohalogenated small molecules have been prepared which can be conjugated with specific functional groups (e.g. amines, sulfhydryl groups, and carbohydrates) or conjugated nonspecifically with groups in the proximity of the conjugate when it is photolyzed. On the basis of previous studies, good conjugation yields (i.e. 60-90%) can be expected for reactions with specific groups, whereas low yields (i.e. 1-5%) can be expected for conjugations with reactive nitrenes and carbenes. However, recent developments in the chemistry of conjugates that produce nitrenes and carbenes will likely improve the radiolabeling yields. There have been too few comparative studies to readily assess which is the best approach to take when beginning a study involving radiohalogenation of a protein or peptide. However, it is clear that radiohalogenated conjugates of proteins can offer an advantage over direct labeling in that conjugates may be designed which provide some control over in vivo stability and secondary distribution of metabolites. Conjugates can be prepared which are designed to utilize in vivo biochemical processes to release a radiohalogenated small molecule from a tissue (i.e. kidney or liver) or retain the radioactivity at the target tissue (e.g. tumor). Aside from the designing of conjugates with linking molecules for desired biological effects, the ultimate future goal for the radiolabeling chemical should be to prepare protein conjugates which can be radiohalogenated in a single one-step procedure.

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Section: Radionuclides Of Halogensmentioning

confidence: 97%

Section: Radiohalogen Labelingmentioning

confidence: 99%

Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

Ds¹

1992

Bioconjugate Chem.

224

176

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“…Radiobromination of Clonidine in the 4-position was possible only in the presence of A1C1 3 as a catalyst [253], whereas α-methyltyrosine was easily labeled with iodine-123 and bromine-75, 77 using chloramine-T in acidic solution [250]. Enzymatic labeling resulted in similar yields, but chloramine-T proved to be superior with respect to the ease of labeling [247,252].…”

Section: Direct Electrophilic Halogenationmentioning

confidence: 99%

“…Radiobrominations have been performed only recently using chloramine-T in aqueous solutions [246][247][248][249][250][251]. Nucleic bases like uracil and cytosine, and amino acids like histidine and tyrosine, were radioiodinated and radio- brominated at an n.c.a.…”

Section: Direct Electrophilic Halogenationmentioning

confidence: 99%

No-Carrier-Added Radiohalogenation Methods with Heavy Halogens

1983

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Radiolabeling methods with the heavy halogens bromine, iodine and astatine are reviewed. The methods are evaluated on the basis of their underlying chemical principles and their usefulness for the no-carrier-added labeling of biologically-useful compounds. Special emphasis is placed on the stability, specific activity, and quality control of radiohalogenation products using the shortlived, neutron-deficient nuclides 7s ' 7 'Br, '"I, and 2 "At in view of their importance as radiopharmaceuticals.

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“…The C-Br bond is stronger than the C-I bond. Therefore the hydrolysis of the C-halogen bond and hence loss of the radiohalogen label may be less important for brominated compounds than for iodinated products [2], Furthermore, any free bromide does not get concentrated in the thyroid or in any other organ, a great advantage when used in human in vivo studies [3].…”

Section: Introductionmentioning

confidence: 99%

Production and Purification of ⁷⁷Br Suitable for Labeling Monoclonal Antibodies Used in Tumor Imaging

Lambert

Slegers

Hermanne³

et al. 1994

Radiochimica Acta

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The irradiation of 400 mg As 2 0 3 with 30 MeV α-particles yields nearly pure "Br resulting from the 75 As (a,2n) 77 Br reaction.y-ray spectroscopy of the irradiated material at EOB + 20 h showed that the radionuclidic purity was >99%. The purification of 77Br from the As 2 0 3 target material is discussed. The irradiated powder is dissolved in boiling water. Anion-exchange column chromatography using Dowex AG 1X8 is performed. The 77 Br is eluted with 1 M NaHSO". The latter is removed by precipitation with methanol. After drying and redissolving the residue in 100 μΐ of water, a 77 Br solution with pH 6-8 is obtained suitable for the labeling of monoclonal antibodies. Recovery experiments with [ 76 As]As 2 0 3 have shown that after anionexchange chromatography less than 10" 5 % of the amount of arsenic is present in the NaHS0 4 aliquot of interest. The chemical state of the radiobromine is checked by 2 methods: HPLC anionchromatography and TLC. Both techniques proved the 77 Br to exist only in the bromide form.

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Rapid radiohalogenations of small molecules—II. Radiobromination of tyrosine, uracil and cytosine

Cited by 15 publications

References 9 publications

Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

No-Carrier-Added Radiohalogenation Methods with Heavy Halogens

Production and Purification of ⁷⁷Br Suitable for Labeling Monoclonal Antibodies Used in Tumor Imaging

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Rapid radiohalogenations of small molecules—II. Radiobromination of tyrosine, uracil and cytosine

Cited by 15 publications

References 9 publications

Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

Radiohalogenation of proteins: An overview of radionuclides, labeling methods and reagents for conjugate labeling

No-Carrier-Added Radiohalogenation Methods with Heavy Halogens

Production and Purification of 77Br Suitable for Labeling Monoclonal Antibodies Used in Tumor Imaging

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Product

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Production and Purification of ⁷⁷Br Suitable for Labeling Monoclonal Antibodies Used in Tumor Imaging