Autoradiographic studies with rhenium-188-HEDP of bone metastases and skeleton

Aim: Dose calculation (MIRDOSE) based on a homogeneous distribution of the radiopharmaceutical in the bone metastases and a 50% uptake in the trabecular and cortical bone. In this study we investigated the uptake in bone metastases and skeleton using autoradiography.
Methods: In previous studies a new model for osteoblastic bone metastases was developedand evidenced by histological examination and bone scan. In 15 Copenhagen rats (age 9 +/- 2 month) 100,000 of MatLyLu R-3327 prostate camcer cells were given intra-osseous. Rhenium-188-HEDP (Re-188-HEDP) i.v. (189 +/- 31 MBq) was administrated 17 +/- 1 days after tumor cell application and 2 days later the animals were killed. By all 15 investigated animals macroscopic tumor mass was visualized. Frozen slices were produced (Cryopolycut, Leica, 40µm thickness) and following autoradiographic studies were performed (BAS 500, FuJi; resolution of 0.5 µm). By means of ROI's the uptake of Re-188-HEDP could be estimated in normal skeleton and bone metastases.
Results: In the bone metastases a tumour to muscle ratio (T/M) of 48 +/- 7 and a tumour to non-tumour ratio (T/NT) of 9.7 +/- 1.5 (7.5 to 11.7) was found. The distribution in the metastases was inhomogeneous with a minimal T/NT of 7.0 +/- 1.0 (4.9 to 8.5) and a maximal T/NT of 17.4 +/- 2.7 (11.6 to 22.6). The ratio between the trabecular and cortical bone in non-tumour bone was 68.6 +/- 7.2% to 31.4 +/- 7.2%.
Conclusion: In the study a high and strong inhomogeneous distribution of bone seeking radiopharmaceutical in bone metastases was found. This fact could favour high beta energy radionuclides for a more homogeneous dose distribution in bone metastases. The MIRDOSE calculation underestimates the bone marrow dose, the uptake in the trabecular bone is higher than in the cortical part. The higher uptake in the trabecular bone decreases the hypothetic dose reduction effect of low beta energy radionuclides to the bone marrow.