Very stable ¹⁸⁸Re-S4 chelates for labelling biomolecules, prepared with highly concentrated perrhenate eluates

Aim:

The preparation and stability of a new ¹⁸⁸Re-S₄-complex (S₄ = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH₂)₃–NH-(CH₂)₃–NHC(O)-C(SH)-C(SH)-C(O)(1-aza-18-crown-6) was studied at therapeutic relevant radioactive concentrations. The results were compared with ¹⁸⁸Re-MAG₃ (MAG₃ = mercaptoacetyltriglycine) and ¹⁸⁸Re-DMSA preparations (DMSA = dimercaptosuccinic acid) performed with the same highly concentrated [¹⁸⁸Re]perrhenate solution (12-15 GBq/ml).

Methods:

The ¹⁸⁸Re complexes were prepared by direct reduction of perrhenate (¹⁸⁸Re-S₄-complex) as well as via the ¹⁸⁸Re-EDTA precursor complex (¹⁸⁸Re-MAG₃, ¹⁸⁸Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes. Results: After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2-8 % of perrhenate was observed after 24 h. In contrast, only the ¹⁸⁸Re-S₄ complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC.

Conclusion:

The bridging amine group or free carboxylic groups of the S₄-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new ¹⁸⁸Re-S₄ complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application.