Bench to bedside development of GMP grade Rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases

Int J Pharm. 2014 Apr 25;465(1-2):317-24. doi: 10.1016/j.ijpharm.2014.01.034. Epub 2014 Feb 19.

Abstract

Bone-targeting therapeutic radiopharmaceuticals are effective agents for treatment of painful bone metastases. Rhenium-188-HEDP is such a therapeutic radiopharmaceutical and has advantages over commercially available alternatives in terms of efficacy, safety and the ability to be produced on-site, allowing rapid treatment upon presentation of patients with pain. Unlike many other radiopharmaceuticals, there are no standardized preparation methods for Rhenium-188-HEDP. It is known, however, that drug composition may not only affect stability of the final drug product, but it may also influence bone affinity and, thus, efficacy. Furthermore, for support of clinical studies with Rhenium-188-HEDP as an investigational medicinal product, preparation of this radiopharmaceutical has to be performed under GMP conditions. To our knowledge, no group has reported on the preparation of Rhenium-188-HEDP under GMP conditions or on stock production of sterile non-radioactive starting materials. We present the production of GMP grade Rhenium-188-HEDP for application of this therapeutic radiopharmaceutical in routine clinical practice and for support of clinical studies. In addition, bio-distribution data of Rhenium-188-HEDP in mice and in patients with bone metastases originating from prostate cancer are presented.

Keywords: Bone metastases; GMP; Prostate cancer; Radionuclide therapy; Rhenium-188; Rhenium-188-HEDP.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Bone Neoplasms / complications
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary*
  • Etidronic Acid / chemical synthesis*
  • Etidronic Acid / pharmacokinetics
  • Etidronic Acid / standards
  • Etidronic Acid / therapeutic use
  • Feasibility Studies
  • Humans
  • Male
  • Mice
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / standards
  • Organometallic Compounds / therapeutic use
  • Pain / etiology*
  • Prostatic Neoplasms / pathology*
  • Quality Control
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / standards
  • Radiopharmaceuticals / therapeutic use
  • Tissue Distribution
  • Translational Medical Research*

Substances

  • Organometallic Compounds
  • Radiopharmaceuticals
  • rhenium-186 HEDP
  • Etidronic Acid