Copper-mediated nucleophilic radiobromination of aryl boron precursors: Convenient preparation of a radiobrominated PARP-1 inhibitor

Abstract

The copper-mediated nucleophilic radiobromination of aryl boron precursors with a radiobromide ion is a novel radiolabeling method that is efficient and robust. High radiochemical conversion (RCC) was observed using a variety of solvents, temperatures and catalysts. The reaction is also clean and is feasible for purification to obtain high chemical and radiochemical purity. This method provides a very useful route for the preparation of radiobrominated pharmaceuticals, including a radiobromine labeled PARP-1 inhibitor, and it is a valuable addition to the family of copper-mediated radiolabeling processes.

Investigation on the reactivity of nucleophilic radiohalogens with arylboronic acids in water: access to an efficient single-step method for the radioiodination and astatination of antibodies

“…12,30 A recent report on radiobromination showed that a substantial proportion of water (up to 50%) can be tolerated for this reaction although high temperatures were still used (80 °C). 31 In this study, we aimed to reinvestigate radioiodination and astatination of arylboronic acids in water, at first on a model compound. We then applied the methodology to the 125 Iradioiodination and 211 At-astatination of an anti-CD138 monoclonal antibody (mAb) that is relevant for targeting multiple myeloma tumour cells.…”

Exploration of alcohol‐enhanced Cu‐mediated radiofluorination toward practical labeling

“…[1][2][3] Boronic acids and esters are probably the most versatile precursors for this radiosynthetic methodology. Besides radiofluorination, copper-mediated nucleophilic radiochemistry using boronic precursors has been used for labeling with other radioisotopes (Br, 4 I, [5][6][7] At, 7 and 11 C 8 ) with great success. For radiofluorination of aromatic compounds, the alcohol-enhanced copper-mediated radiofluorination appears to be the most favorable one for achieving high radiochemical conversions (RCCs).…”

PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response

“…Recently, poly (ADP-ribose) polymerase (PARP) targeted beta and Auger emitting radiopharmaceuticals have been reported for the treatment of glioblastoma and showed anti-tumor effects both in-vitro and in-vivo [ 8 , 9 ]. Furthermore, other bromine-77 PARP inhibitors have been reported, although pre-clinical evaluation is ongoing [ 10 , 11 ].…”