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The development of the rhenium-188 generator has provided a convenient and economic source of radionuclide for targeted radionuclide therapy of cancer. To exploit this more widely, mild, convenient and efficient methods for stable incorporation of the radionuclide into biomolecules are required. The aim of this work is to exploit the tumour targeting therapeutic radiopharmaceutical [ReO(dmsa) 2 ] Ϫ (H 2 dmsa = meso-dimercaptosuccinic acid), which is easily synthesised in radioactive form and highly stable in vivo, for this purpose. A new efficient synthesis of [ReO(dmsa) 2 ] Ϫ , as a single isomer (syn-endo), from perrhenate using acetylhydrazine as reductant, is reported. Dehydration of the two dicarboxylic acid groups of [ReO(dmsa) 2 ] Ϫ with dicyclohexylcarbodiimide gives the yellow cyclic dianhydride [ReO(dmsaa) 2 ] Ϫ (H 2 dmsaa = meso-dimercaptosuccinic anhydride) without disrupting the ReOS 4 core. As its tetraethylammonium salt, [ReO(dmsaa) 2 ] Ϫ was characterised crystallographically as a distorted square pyramidal complex with an axial oxo-group and a syn-endo orientation of the two anhydride rings with respect to this oxo-group. [ReO(dmsaa) 2 ] Ϫ reacts with primary and secondary amines including lysine residues of peptides, to form amide-linked conjugates, which were identified by ES-MS. The syntheses are fast, efficient and employ mild conditions, making them readily adaptable for a kit-based approach to rhenium and technetium radiopharmaceuticals.

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