[en] MDP (methylenediphosphonate) and HEDP (hydroxyethylidenediphosphonate), both diphosphonates, and EDTMP (ethylenediamine tetramethylene phosphonic acid) a tetraphosphonate ligand, have been labeled with ¹⁸⁸Re for use in metastatic bone-pain palliation. The aim of this study was a comparison between the three complexes ¹⁸⁸Re-MDP, ¹⁸⁸Re-HEDP and ¹⁸⁸Re-EDTMP concerning the complexation conditions, in order to achieve maximum yield, stability and bone uptake. Methods: MDP was dissolved in water and HEDP and EDTMP were dissolved in NaOH 1N followed by decreasing pH with HCl 1N. To all mixtures stannous chloride and ¹⁸⁸ReO₄ were added in a nitrogen atmosphere. The preparations were heated in a boiling water bath for 15 min. The yields as well as the radiochemical stability were estimated by ITLC. Different concentrations of phosphonates and stannous chloride were evaluated. Biodistribution studies in swiss mice were done for the three ¹⁸⁸Re-phosphonates that presented the best radiochemical yield. Results: For ¹⁸⁸Re-MDP and ¹⁸⁸Re-HEDP the optimal ligand concentration for maximum complexation was 30 mg whereas for ¹⁸⁸Re-EDTMP, it was 40 mg. The best amount of SnCl₂.2H₂O was 2 mg/mL for MDP, 3 mg/mL for HEDP and 1 mg/mL for EDTMP. In these conditions the three complexes showed a complexation yield above 95%. All of them presented 4-hour radiochemical stability without the need for ascorbic acid solution, but for 24 hours this stability existed only in the presence of that substance otherwise re-oxidation of ¹⁸⁸Re occurred. All products showed a great uptake by the kidneys. ¹⁸⁸Re-EDTMP had the greatest uptake by the bone (3.13 ± 0.18% ID/g) followed by ¹⁸⁸Re-MDP (1.18 ± 0.05%ID/g) and ¹⁸⁸Re-HEDP (1.03 ± 0.12 %ID/g), 4 hour postinjection. ¹⁸⁸Re-EDTMP displayed a bone/muscle ratio of 28.5, ¹⁸⁸Re-MDP 4.9 and ¹⁸⁸Re-HEDP 4.9. Conclusion: ¹⁸⁸Re-EDTMP demonstrated the best potential as a radiopharmaceutical for bone cancer pain relief, encouraging further dosimetric studies and clinical trials