title: 99mTc(CO)3-labeled pamidronate and alendronate for bone imaging.
abstract: Bone scintigraphy with (99m)Technetium-methylenediphosphonate ((99m)Tc-MDP) or (99m)Technetium-hydroxymethylenediphosphonate ((99m)Tc-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-[(99m)Tc(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-[(99m)Tc(CO)(3)](+) yielded (> 95%) the stable complexes fac-[(99m)Tc(CO)(3)(pz-PAM)](-) (2a) and fac-[(99m)Tc(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 (99m)Tc-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 (99m)Tc-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 (99m)Tc-MDP (70.9, 47.9), at 4 h post injection. Planar whole-body gamma camera images of the rats injected with the (99m)Tc(CO)(3)-labeled pamidronate (2a) and alendronate (3a) confirmed the overall adequate biological profile of the new radiotracers for bone imaging.
authors.affiliation: Unidade de Ciências Químicas e Radiofarmacêuticas, ITN, Estrada Nacional 10, 2686-953 Sacavém, Portugal.
authors.forename: Elisa
authors.initials: E
authors.lastname: Palma
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Oliveira
authors.forename: Lurdes
authors.initials: L
authors.lastname: Gano
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Santos
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
mesh_terms: D019386:Alendronate / Q000737:chemistry*; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D018360:Crystallography, X-Ray; D004164:Diphosphonates / Q000737:chemistry*; D005260:Female; D051379:Mice; D008968:Molecular Conformation; D000077268:Pamidronate; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D004164:Diphosphonates; D019275:Radiopharmaceuticals; D013667:Technetium; D000077268:Pamidronate; D019386:Alendronate