Abstract
BACKGROUND: The hypothetical concept of 'macrocyclic cavity' is largely employed as useful model to interpret the affinity of metal ions for the macrocyclic chelating ligand 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (H(4)DOTA). It Is hypothesized that a close matching between the size of the macrocyclic cavity and that of the metallic ion is a key parameter to ensure the high-yield formation of stable coordination metal-DOTA complex. This approach has become popular in the design of radiopharmaceuticals containing radiometals and H(4)DOTA as chelating group. RESULTS: Based on X-ray structural data of metallic complexes formed by the ligand H(4)DOTA upon coordination with a variety of metals, an elementary argument based on Euclidean geometry is presented here that questions the existence of the hypothetical 'macrocyclic cavity' within the chelator macrocycle. The geometrical analysis was applied to the complex formed by a Ga(3+) ion coordinated to H(4)DOTA as model compound. CONCLUSIONS: Application of Euclidean geometry to calculate bond angles in the coordination complex of the ligand H(4)DOTA with the Ga(+3) ion, supposed to incorporate a hypothetical 'macrocyclic cavity', revealed that this conceptual entity has no physical reality and, therefore, cannot be considered a meaningful description of a stable structural arrangement for metallic radiopharmaceuticals.