| Abstract |
Bone scintigraphy with (99m)Technetium-methylenediphosphonate (Tc-99m-MDP) or (99m)Technetium-hydroxymethylenediphosphonate (Tc-99m-HMDP) presents several limitations, namely low specificity, uncertainty in the radiopharmaceutical s molecular structure and long acquisition time after injection. Aiming to find bone-seeking radiotracers based on the core fac-[Tc-99m(CO)(3)](+) with improved chemical and biological properties, we synthesized new conjugates (pz-PAM and pz-ALN), comprising a pyrazolyl-diamine chelating unit (pz: N,N,N donor atom set) for metal stabilization and a pendant pamidronate (PAM) or alendronate (ALN) moiety for bone targeting. The reaction of the conjugates with fac-[Tc-99m(CO)(3)](+) yielded (> 95\%) the stable complexes fac-[Tc-99m(CO)(3)(pz-PAM)](-) (2a) and fac-[Tc-99m(CO)(3)(pz-ALN)] (3a), which have been characterized by comparing their HPLC gamma-traces with the UV-vis traces of the Re surrogates 2 and 3, respectively. 2a and 3a bind strongly onto hydroxyapatite. The biodistribution studies in Balb-c mice have shown that 2a and 3a presented an high bone uptake (2a 18.3 +/- 0.6\% I.D./g, 3a 17.3 +/- 6.1\% I.D./g, at 1 h post injection), similar to Tc-99m-MDP (17.1 +/- 2.4\% I.D./g, at 1 h post injection), with comparable clearance from most tissues and increased total excretion (2a 66\% I.D., 3a 67\% I.D. and Tc-99m-MDP 49\% I.D., at 1 h post injection). The bone-to-blood (2a 86.2, 3a 74.7) and the bone-to-muscle ratios (2a 77.7, 3a 79.0) are higher than the ones found for Tc-99m-MDP (70.9, 47.9), at 4 h post injection. Planar whole-body gamma camera images of the rats injected with the Tc-99m(CO)(3)-labeled pamidronate (2a) and alendronate (3a) confirmed the overall adequate biological profile of the new radiotracers for bone imaging. |
