Carborane-carbohydrate derivatives — Versatile platforms for developing targeted radiopharmaceuticals

Abstract

A series of carborane-carbohydrate derivatives were prepared as model platforms for developing targeted radiopharmaceuticals in which a single ligand can be tagged with two different classes of radionuclides. A nido-carborane linked to glucose was synthesized and the cage labelled with a radiometal (99mTc) and a radiohalogen (125I) in good radiochemical yield. The 99mTc-metallocarborane derivative was prepared via microwave-assisted reactions, while the iodinated derivative was prepared using oxidative labelling methods in mere minutes. Fully characterized reference standards were prepared using nonradioactive rhenium and iodine and used to demonstrate that the isolated radioactive compounds were in fact the desired targets. The work reported, which is one of the rare examples of a single ligand system that can be labelled with both radiohalogens and radiometals, forms the basis of a new paradigm for developing targeted radiopharmaceuticals.Key words: carboranes, medical isotopes, technetium-99m, iodine-125, glucose.

Carbohydrate‐Based Molecules for Molecular Imaging in Nuclear Medicine

“…Much of the attractiveness of this tricarbonyl core lies in its high kinetic inertness and stability to oxidation in biological environments. Over the last decade, a number of saccharides have been labeled with this organometallic fac ‐[ 99m Tc(CO) 3 ] + core, with the aid of different bi‐ (compounds 41 and 42 , Figure 11) and tridentate (compounds 43 – 46 ), Werner‐type chelators,67 cyclopentadienyl systems (e.g., 47 ),67k,68 and carborane 69. The small size of this organometallic core means that it does not interfere with the biological activities of small molecules such as glucose.…”

Synthesis and screening of bifunctional radiolabelled carborane-carbohydrate derivatives

“…We recently described the preparation and labelling of simple carboranyl glycoside derivatives of glucose with both Tc and iodine [44,45]. Building on the success of the model system, a nido-carboranyl glycoside 1 that contains a benzoic acid group for conjugation to targeting vectors such as peptides, proteins, or antibodies was developed (Fig.…”

“…The radiolabelling of compounds 1, 7, and 8 was undertaken following methods previously established for radioiodination of the simple carboranyl glycoside derivative [45]. Compound [ 125 I]-14 was prepared and isolated via HPLC in 50% radiochemical yield.…”

New developments in the medicinal chemistry of carboranes

“…The fully characterized nonradioactive rhenium and iodinated compounds were used as the reference standards to demonstrate that the isolated radioactive compounds were indeed the desired target compounds. This work demonstrated the advantage of using carborane ligand system which can be labelled with both radiohalogens and radiometals and thus can be potentially useful in developing targeted radiopharmaceuticals 77 . A number of other radiohalogen ( 125 I) containing water-soluble carboranyl derivatives containing glucose, benzoic acid and polyamine moieties, 63-65, were also developed as potential molecular radioimaging and therapy agents 78 .…”