An Inorganic Building Block for Preparing Molecular Imaging and Therapy Agents

Carboranes are polyhedral clusters composed of BH and CH units that range in size from the small trigonal bipyramidal H2C2B3H6 cluster to substantially larger compounds. Among these, the most familiar molecule is the icosahedral dicarbadodecaborane H2C2B10H10 better known as closo-ortho-carborane, or simply "carborane" (shown below).


The carborane unit is an attractive synthon for radiopharmaceuticals for several reasons. First, it can readily be derivatized at one or both of the CH verticies (or at a BH vertex): the substituent introduced may be a biologically active moiety that acts as a targeting vector, or a simple functional group that that modifies physical properties such as solubility. In addition, carborane derivatives are generally stable in water; this is a key property because radiopharmaceuticals must be compatible with aqueous media in order to be administered in vivo.


Though closo-carboranes cannot be radiolabelled readily, they are easily converted to the more suitable nido- species via boron atom abstraction in the presence of a base (see above). The anionic nido-carborane is a fascinating molecule from a nuclear medicine standpoint because it forms stable complexes with both halogens and the ubiquitous radiometal technetium-99m and its heavier congener rhenium. Due to the diverse nuclear properties of the numerous radiohalogen isotopes, the carborane unit can serve as a platform for the preparation of PET (18F, 75Br, 76Br, 122I, 124I) imaging agents, SPECT (123I, 99mTc) imaging agents, and radiotherapeutic agents (125I, 131I, 186/188Re).



Members of our research group are currently exploring various aspects of carborane chemistry and incorporating this research into the design of new radio-pharmaceuticals.


For a recent discussion of carboranes in medicinal chemistry, see A. F. Armstrong, J.F. Valliant Dalton Trans. (Perspectives), 2007, 4240-4251.