Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [99mTc], [111In], [153Sm] and [188Re] on bone compartments: verification of the pre vivo model?

Introduction: Although the first polyphosphonates (PP) were introduced to nuclear medicine as bone imagers in the early 70s, mechanisms involved in uptake still remain speculative. Controversies range from adsorption onto the mineral phase with disputed binding to the organic phase, over incorporation into the mineralisation process to a combination of both mechanisms. Other factors such as solubility of the complex, concentration of ligand or effects of the radionuclide have also been discussed as possible parameters influencing bone uptake. Therefore, the present work aimed to verify the recently presented pre vivo model which was developed to rate the influence of various factors on the binding of differently radiolabelled PP and [18F]-fluoride on synthetic bone matrix.

Methods: Radiolabelled polyphosphonates and [18F]-fluoride were added to a vial containing lyophilised and milled spongiosa (Sp) or cortical bone (Co) in Hank's Balanced Salt Solution. After incubation, the radioactivity was measured in the gamma-counter before and after filtration. The percentage of irreversibly bound radioactivity was calculated. Same experiments were performed after decalcification of Sp and Co with hydrochloric acid.

Results: Descriptively, [111In] increases the uptake of EDTMP in each case compared to similarly prepared [(99m)Tc]-analogues: [111In]-EDTMP > [(99m)Tc]-EDTMP, [111In]-/In-EDTMP > [(99m)Tc]-/In-EDTMP and [111In]-/Re-EDTMP > [(99m)Tc]-/Re-EDTMP. [188Re]-EDTMP shows higher binding than the carrier-added analogue, contradicting recent in vivo findings of [(188)Re]-PP. However, our findings on human matrix are consistent with those of a previous study using artificial bone material. Binding on decalcified tissue was very low (PP) to moderate ([18F]-fluoride) and reversible. Remarkable is also the unrivalled high uptake of [18F]-fluoride, showing no reduced uptake on Co and Sp as compared to hydroxyapatite (HA) and amorphous calcium phosphate (ACP).

Conclusion: The binding of the evaluated bone seekers on these human bone matrices follows a comparable pattern as on artificial bone. The present study substantiates the fact that binding predominantly occurs on the inorganic compartment of bone. The best correlation was found between HA and Co. Therefore, HA can serve as a matrix for representative binding studies.