Straightforward synthesis of radioiodinated Cc-substituted o-carboranes: towards a versatile platform to enable the in vivo assessment of BNCT drug candidates

Due to their high boron content and rich chemistry, dicarba-closo-dodecaboranes (carboranes) are promising building blocks for the development of drug candidates with application in Boron Neutron Capture Therapy. However, the non-invasive determination of their pharmacokinetic properties to predict therapeutic efficacy is still a challenge. Herein, we have reported the unprecedented preparation of mono-[I-125] iodinated decaborane via a catalyst-assisted isotopic exchange. Subsequent reactions of the radiolabelled species with acetylenes in acetonitrile under microwave heating yield the corresponding I-125-labelled, C-c-substituted o-carboranes with good overall radiochemical yields in short reaction times. The same synthetic strategy was successfully applied to the preparation of I-131-labelled analogues, and further extension to other radioisotopes of iodine such as I-124 (positron emitter) or I-123 (gamma emitter) can be envisaged. Hence, the general strategy reported here is suitable for the preparation of a wide range of radiolabelled C-c-substituted o-carborane derivatives. The labelled compounds might be subsequently investigated in vivo by using nuclear imaging techniques such as Single Photon Emission Computerized Tomography or Positron Emission Tomography.