125215-73-8Relevant articles and documents
Bifunctional aryliodonium salts for highly efficient radioiodination and astatination of antibodies
Guérard,Navarro,Lee,Roumesy,Alliot,Chérel,Brechbiel,Gestin
, p. 5975 - 5980 (2017)
In this report we describe the development of an alternative approach to arylstannane chemistry for radiolabeling antibodies with radioiodine or astatine based on aryliodonium salts precursors. Bifunctional aryliodonium salts were designed and tested for the synthesis of 125I and 211At labeled prosthetic groups for bioconjugation. The nature of the electron rich aryl group was varied and its impact on the regioselectivity of radiohalogenation was evaluated. Unexpectedly, whereas the 2-thienyl group provided the best regioselectivity towards the radioiodination of the aryl moiety of interest (98:2), it was less selective for astatination (87:13); the anisyl group providing the best regioselectivity of astatination (94:6). Under optimized conditions, both radioiodination and astatination could be performed very efficiently in mild conditions (radiochemical yields > 85%). The ionic nature of the precursors was exploited to develop an efficient purification approach: the HPLC step that is usually necessary in conventionnal approaches to optimize removal of organotin toxic precursors and side products was replaced by a filtration through a silica cartridge with a significantly reduced loss of radiolabeled product. The purified radioiodinated and astatinated prosthetic groups were then conjugated efficiently to an anti-CD138 monoclonal antibody (75–80% conjugation yield). By using this novel and simple radiohalogenation procedure, higher overall radiochemical yields of astatination were obtained in comparison with the use of an arylstannane precursor and procedures of the litterature for labeling the same antibody. Overall, due to their simplicity of use and high robustness, these new precursors should simplify the labeling of proteins of interest with iodine and astatine radioisotopes for imaging and therapeutic applications.
Polymer-supported organotin reagent for prosthetic group labeling of biological macromolecules with radioiodine
Gifford, Andrew N.,Kuschel, Sonja,Shea, Colleen,Fowler, Joanna S.
, p. 406 - 412 (2011)
In this study, we investigated the use of poly-mer-bound precursor for generating a radiolabeled prosthetic group to be used for conjugate labeling of biological macromolecules. For the approach, a trialkyltin chloride in which the tin was bound to a hydrophilic PEG-based resin support via one of the alkyl groups was synthesized. This resin was then used to prepare a resin-bound trialkyltin benzoic acid, which in some cases was further derivatized on-resin by converting it to a succinimidyl ester. Exposure of the resin-bound compounds to electrophilic radioiodine (125I) in either an aqueous or methanol solvent liberated either free radiolabeled [125I]iodobenzoic acid or its succinimidyl ester without co-release of the resin-bound precursors. Radiochemical yield was between 35% and 75%, depending on the solvent system and precursor. As example applications for the released compounds, the amine-reactive N-succinimidyl-[125I]iodobenzoate prosthetic group was used for conjugate radiolabeling of a peptide, tomato plant systemin, and two proteins, albumin and IgG antibody. These results demonstrate that resin-bound organotin precursors in which the compound to be labeled is tethered to the support via the tin group to be substituted can be used to produce radioiodine-labeled aromatic prosthetic groups in good specific activity without the need for HPLC purification. This solid-phase approach is potentially adaptable to kit-formulation for performing conjugate radiolabeling of biological macromolecules.
Comparison of radioiodine- or radiobromine-labeled rgd peptides between direct and indirect labeling methods
Ogawa, Kazuma,Takeda, Takuya,Yokokawa, Masaru,Yu, Jing,Makino, Akira,Kiyono, Yasushi,Shiba, Kazuhiro,Kinuya, Seigo,Odani, Akira
, p. 651 - 659 (2018/06/11)
Radiolabeled cyclic peptides containing the (Arg-Gly-Asp) RGD sequence for use in positron emission tomography (PET) imaging, single-photon emission computed tomography (SPECT) imaging, and targeted radionuclide therapy of cancer have been reported. In this study, RGD was used as a model carrier peptide for diagnosis and therapy of cancer. To evaluate the characteristics of radiohalogen-labeled peptides, several kinds of labeled RGD peptides [125I-c(RGDyK), 77Br-c(RGDyK), [125I]SIB-c(RGDfK), [77Br]SBrB-c(RGDfK), [125I]SIB-EG2-c(RGDfK), and [77Br]SBrB-EG2-c(RGDfK)] were designed, prepared, and evaluated. In these initial studies, 77Br (t1/2=57.0h) and 125I (t1/2=59.4d) were used because of their longer half-lives. Precursor peptides were synthesized using a standard 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase methodology. Radiolabeled peptides were prepared by chloramine-T method or conjugation of RGD peptides with [125I]N-succinimidyl 3-iodobenzoate ([125I]SIB) or [77Br]N-succinimidyl 3-bromobenzoate ([77Br]SBrB). Measurement of the partition coefficients, integrin binding assay, and biodistribution experiments in tumor-bearing mice were performed. 125I and 77Br labeling were successfully performed using similar methods, and in vitro characteristics and biodistributions were similar between the 125I-labeled and corresponding 77Br-labeled peptides. [125I]SIB- and [77Br]SBrB-conjugated RGD peptides showed higher partition coefficients, lower tumor uptakes, and higher intestinal uptake than 125I-c(RGDyK) and 77Br-c(RGDyK). [125I]SIB-EG2-c(RGDfK) and [77Br]SBrB-EG2-c(RGDfK), which possess an ethylene glycol linker, decreased lipophilicity and uptake in intestine compared with [125I]SIB-c(RGDfK) and [77Br]SBrB-c(RGDfK), which possess no linker. However, the improvement in biodistribution of [125I]SIB-EG2-c(RGDfK) and [77Br]SBrB-EG2-c(RGDfK)] was insufficient. In conclusion, directly radiohalogenated c(RGDyK) peptides are potentially more useful for tumor imaging and therapy than indirectly radiohalogenated ones.
Ionic liquid supported organotin reagents to prepare molecular imaging and therapy agents
Rajerison, Holisoa,Faye, Djibril,Roumesy, Aurélia,Louaisil, Nicolas,Boeda, Fabien,Faivre-Chauvet, Alain,Gestin, Jean-Fran?ois,Legoupy, Stéphanie
, p. 2121 - 2126 (2016/02/18)
Efficiency of ionic liquid supported organotin reagents in halodemetalation reaction has been investigated. High radiochemical yields of astatinated and iodinated compounds have been obtained using simple work-up procedure. This methodology represents a s
