Rhemium-186-1-hydroxyethylidene-1,1-diphosphonate ((186)Re-HEDP) has been used for the palliation of metastatic bone pain. However, delayed blood clearance and high gastric uptake of radioactivity have been observed upon injection, due to the instability of (186)Re-HEDP. We designed, synthesized and evaluated a stable (186)Re-mercaptoacetylglycylglycylglycine (MAG3) complex-conjugated bisphosphonate, [[[[(4-hydroxy-4,4-diphosphonobutyl)carbamoylmethyl] carbamoylmethyl]carbamoylmethyl]carbamoylmethanethiolate] oxorhenium(V) ((186)Re-MAG3-HBP). The stability of (186)Re-MAG3-HBP and (186)Re-HEDP in phosphate buffer were compared. No measurable decomposition of (186)Re-MAG3-HBP occurred, while only approximately 30% of (186)Re-HEDP remained intact 24 hours post-incubation. In biodistribution experiments, the radioactivity level of (186)Re-MAG3-HBP in bone was significantly higher than that of (186)Re-HEDP. Blood clearance of (186)Re-MAG3-HBP was faster than that of (186)Re-HEDP. In addition, the gastric accumulation of (186)Re-MAG3-HBP radioactivity was lower. To evaluate the therapeutic effects of (186)Re-MAG3-HBP, an animal model of bone metastasis was prepared. In the rats treated with (186)Re-HEDP, tumor growth was comparable to that in untreated rats. In contrast, when (186)Re-MAG3-HBP was administered, tumor growth was significantly inhibited. Bone pain was attenuated by treatment with (186)Re-MAG3-HBP or (186)Re-HEDP, but (186)Re-MAG3-HBP tended to be more effective. These results indicate that (186)Re-MAG3-HBP could be useful as a therapeutic agent of metastatic bone pain. Moreover, based on the similar concept, we designed, synthesized, and evaluated a (99m)Tc-6-hydrazinopyridine-3-carboxylic acid-conjugated bisphosphonate ((99m)Tc-HYNIC-HBP) as a bone scintigraphic agent. (99m)Tc-HYNIC-HBP gave higher levels of radioactivity in bone than (99m)Tc-HMDP. There was no significant difference in clearance from blood between (99m)Tc-HYNIC-HBP and (99m)Tc-HMDP. Consequently, (99m)Tc-HYNIC-HBP showed a higher bone-to-blood ratio than (99m)Tc-HMDP. The findings indicate that (99m)Tc-HYNIC-HBP holds great potential for bone scintigraphy.