title: 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.
abstract: BACKGROUND
  (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.
  
  
  CONCLUSIONS
  Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo.
  
  
  CONCLUSIONS
  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.
authors: Meander Medical Center, Department of Clinical Pharmacy, Amersfoort, The Netherlands.
authors: R
authors: R
authors: Lange
authors: Meander Medical Center, Department of Radiology & Nuclear Medicine, Amersfoort, The Netherlands.
authors: J M H
authors: JMH
authors: de Klerk
authors: Meander Medical Center, Department of Internal Medicine, Amersfoort, The Netherlands.
authors: H J
authors: HJ
authors: Bloemendal
authors: Section Radiation, Detection & Medical Imaging, TU Delft & MILabs B.V., Utrecht, The Netherlands.
authors: R M
authors: RM
authors: Ramakers
authors: Section Radiation, Detection & Medical Imaging, TU Delft & MILabs B.V., Utrecht, The Netherlands.
authors: F J
authors: FJ
authors: Beekman
authors: Meander Medical Center, Department of Pharmacy, Amersfoort, The Netherlands.
authors: M M L
authors: MML
authors: van der Westerlaken
authors: Department of Clinical Pharmacology & Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
authors: N H
authors: NH
authors: Hendrikse
authors: Meander Medical Center, Department of Clinical Pharmacy, Maatweg 3, 3813TZ, Amersfoort, The Netherlands. Electronic address: rob@terheine.nl.
authors: R
authors: R
authors: Ter Heine
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012968:Etidronic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011854:Radiochemistry / Q000379:methods*; D011868:Radioisotopes / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012211:Rhenium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D017886:Durapatite; D012968:Etidronic Acid
keywords: Bone affinity; Hydroxyapatite; Rhenium-188; Rhenium-188-HEDP; Rhenium-HEDP