Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP

Nucl Med Biol. 2015 May;42(5):465-469. doi: 10.1016/j.nucmedbio.2015.01.007. Epub 2015 Jan 22.


Introduction: (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration.

Methods: We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice.

Results: The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP.

Conclusions: For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs.

Advances in knowledge: Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo.

Implications for patient care: The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided.

Keywords: Bone affinity; Hydroxyapatite; Rhenium-188; Rhenium-188-HEDP; Rhenium-HEDP.

MeSH terms

  • Animals
  • Bone and Bones / metabolism
  • Durapatite / chemistry*
  • Durapatite / pharmacokinetics
  • Durapatite / therapeutic use
  • Etidronic Acid / chemistry*
  • Etidronic Acid / pharmacokinetics
  • Etidronic Acid / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Radiochemistry / methods*
  • Radioisotopes / chemistry*
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Rhenium / chemistry*
  • Tissue Distribution


  • Radioisotopes
  • Radiopharmaceuticals
  • Rhenium
  • Durapatite
  • Etidronic Acid