title: Bench to bedside development of GMP grade Rhenium-188-HEDP, a radiopharmaceutical for targeted treatment of painful bone metastases.
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.
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands. Electronic address: rob@terheine.nl.
authors.forename: Rob
authors.initials: R
authors.lastname: ter Heine
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Lange
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Oscar B
authors.initials: OB
authors.lastname: Breukels
authors.affiliation: Department of Internal Medicine, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Haiko J
authors.initials: HJ
authors.lastname: Bloemendal
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Rob G
authors.initials: RG
authors.lastname: Rummenie
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Antoinette M
authors.initials: AM
authors.lastname: Wakker
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Hilly
authors.initials: H
authors.lastname: de Graaf
authors.affiliation: Section Radiation, Detection & Medical Imaging, TU Delft & MILabs B.V., Utrecht, The Netherlands.
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Beekman
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Monique M L
authors.initials: MM
authors.lastname: van der Westerlaken
authors.affiliation: Department of Clinical Pharmacy, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Mirte M
authors.initials: MM
authors.lastname: Malingré
authors.affiliation: Department of Clinical Chemistry, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Jos P M
authors.initials: JP
authors.lastname: Wielders
authors.affiliation: Department of Radiology & Nuclear Medicine, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: van den Berg
authors.affiliation: Department of Clinical Pharmacology & Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
authors.affiliation: Department of Radiology & Nuclear Medicine, Meander Medical Center, Amersfoort, The Netherlands.
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary*; D012968:Etidronic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use; D010146:Pain / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000592:standards / Q000627:therapeutic use; D014018:Tissue Distribution; D057170:Translational Research, Biomedical
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C101598:rhenium-186 HEDP; D012968:Etidronic Acid
keywords: Bone metastases; GMP; Prostate cancer; Radionuclide therapy; Rhenium-188; Rhenium-188-HEDP