Kinetics and Thermodynamics of Adsorption on Hydroxyapatite of the [¹⁶⁰Tb]Terbium Complexes of the Bone-Targeting Ligands DOTP and BPPED

Abstract

The temperature-dependent adsorption on hydroxyapatite (HAP) of the Tb complexes of two macrocyclic DOTA-like ligands containing HAP-binding phosphonate groups was studied by a radiotracer method using 160Tb as the label. One ligand (DOTP) contains four separate phosphonate groups, while the second ligand (BPPED) contains a single bisphosphonate group coupled via a phosphinate spacer group. The equilibrium isotherms were fitted by models according to Langmuir, Freundlich, Langmuir-Freundlich, Toth, and Dubinin-Radushkevich, with the Langmuir-Freundlich and the Toth models resulting in the best fits. These models take into account the energetic surface heterogeneity of HAP for the binding of the complexes, which was confirmed by the dependence of the reversibility of the adsorption on the complex concentration. The affinity of the Tb-BPPED complex toward the HAP surface was substantially higher than that of the Tb-DOTP complex. Thermodynamic parameters obtained from the temperature-dependence of the adsorption and the Van't Hoff relation showed that the adsorption of both complex types is endothermic and entropy-driven, due to dehydration of the complex and the HAP surface during adsorption. The kinetics of the adsorption were very fast, and of the tested models (pseudo-first-order, pseudo-second-order, intraparticle diffusion, and Elovich) only the Elovich model described the experimental data suitably. The activation energy of the adsorption was calculated by application of an Arrhenius-type relation, showing chemisorption for both complex types. Adsorption rates were reduced when HAP with larger particle size was used.

Controlled adsorption and release onto calcium phosphates materials and drug delivery applications

“…Thus, Rill and al. [10] determined the thermodynamic parameters of hydroxyaptite interaction with some complexes containing functional molecules and showed that the process is endothermic and entropy-driven, due to the release of water molecules from the solubilized complexes as well as from the polar apatite surface upon adsorption. A similar dependence on temperature was previously reported for the uptake of phosphoproteins by hydroxyapatite [11].…”

Chelating agents for radiolanthanides: Applications to imaging and therapy

“…High radiolabelling efficiencies (>98%) were reported for each ligand and it was noted that the 153 Sm/ 166 Ho-TRITP complexes bound to hydroxyapatite, which manifested in good bone uptake in corresponding biodistribution studies. 67 In an unrelated study, 160 Tb has been used for the physical study of the adsorption of lanthanide complexes to hydroxyapatite; 67 complexes of the phosphonate ligands DO3A BP and DOTP were studied. Adsorption was found to be very fast for both complexes, with the 160 Tb-DO3A BP complex showing a greater affinity for the hydroxyapatite surface than 160 Tb-DOTP, presumably due to the availability of the pendant bisphosphonate group.…”

“…9) and were originally developed by Parker and co-workers more than 20 years ago. 76 The original design of such systems was to address the chelation of 67 Ga and 111 In based radiopharmaceuticals (Table 1) However, more recent progress has shown that stable Ln(III) complexes can be achieved through functionalisation of the TACN framework with dipicolinate arms (Fig. 10).…”

“…The radiolabelling of porphyrins in nuclear medicine has been reviewed elsewhere, 94 highlighting the large number of metallo-radionuclides that have been investigated in this context, including 99m Tc, 57 Co, 64 Cu, 67 Ga, 68 Ga, 109 Pd, 111 In, 209 Pb and 213 Bi. The first metalloporphyrins based on lanthanides were synthesised in the 1970s 95 and were initially investigated as shift reagents in NMR.…”

“…These include the single gamma photon emitting isotopes 99m Tc, 67 Ga and 111 In (see Table 1) that are employed in gamma photography techniques, 1 such as 67 Ga scintigraphy (a 'gallium' scan) and singlephoton emission computed tomography (SPECT); currently 99m Tc accounts for approximately 80% of all nuclear medicine procedures where ( 99m Tc-tetrofosmin for cardiac perfusion). In positron emission tomography (PET), β + emission followed by electron annihilation results in the emission of collinear gamma rays, a method dominated by widely available 18 F tracers (e.g.…”