Bone uptake studies in rabbits before and after high-dose treatment with Sm-153-EDTMP or Re-186-HEDP

The aim of this animal study was to measure the bone uptake of Tc-99m-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with 153Sm-ethylenediaminetetramethylene-phosphonate (EDTMP) or Re-186-(tin)1,1 -hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. Methods: Quantitative bone scanning using 100 MBq Tc-99m-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either Sm-153-EDTMP or Re-186-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. Results: In animals treated with Sm-153-EDTMP (n = 6), no differences could be proven for the bone uptake of Tc-99m-HDP at 24 h after injection before and after therapy (51.1% +/- 5.5% vs. 48.0% +/- 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with 186Re-HEDP: Bone uptake (44.8% +/- 6.7% vs. 40.4% +/- 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. Conclusion: No significant impairment of bone uptake of 99mTc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for 186Re-HEDP and 153Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2-3 mo after standard treatment with Re-186-HEDP or Sm-153-EDTMP.