title: Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.
abstract: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with188Re in prostate carcinoma cell lines.
  
  
  
  The cytotoxic effects of single and combined treatment with taxanes and188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model.
  
  
  
  The survival curves showed dose-dependent cell growth inhibition for both the taxanes and188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect.
  
  
  
  This proof-of-mechanism study exploring radiosensitization by combining188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and188Re-HEDP.
authors.affiliation: 1 Department of Clinical Pharmacy, Meander Medical Center , Amersfoort, The Netherlands .
authors.forename: Rogier
authors.initials: R
authors.lastname: Lange
authors.affiliation: 2 Department of Pharmacy, Radboud University Medical Center , Nijmegen.
authors.forename: Rob
authors.initials: R
authors.lastname: ter Heine
authors.affiliation: 3 Department of Epidemiology and Biostatistics, VU University Medical Center , Amsterdam, The Netherlands .|4 Department of Mathematics, VU University , Amsterdam, The Netherlands .
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.affiliation: 5 Department of Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands .
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Tromp
authors.affiliation: 5 Department of Pharmaceutical Sciences, Utrecht University , Utrecht, The Netherlands .
authors.forename: Mayke
authors.initials: M
authors.lastname: Paap
authors.affiliation: 6 Department of Internal Medicine/Medical Oncology, Meander Medical Center , Amersfoort, The Netherlands .|7 Department of Medical Oncology, University Medical Center , Utrecht, The Netherlands .
authors.forename: Haiko J
authors.initials: HJ
authors.lastname: Bloemendal
authors.affiliation: 8 Department of Nuclear Medicine, Meander Medical Center , Amersfoort, The Netherlands .
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
authors.affiliation: 9 Department of Clinical Pharmacology and Pharmacy, VU University Medical Center , Amsterdam, The Netherlands .|10 Department of Radiology and Nuclear Medicine, VU University Medical Center , Amsterdam, The Netherlands .
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
authors.affiliation: 11 Department of Urology, VU University Medical Center , Amsterdam, The Netherlands .|12 Department of Radiology and Nuclear Medicine, VU University Medical Center , Amsterdam, The Netherlands .
authors.forename: Albert A
authors.initials: AA
authors.lastname: Geldof
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D017024:Chemotherapy, Adjuvant; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D012968:Etidronic Acid / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D043823:Taxoids; C101598:rhenium-186 HEDP; D000077143:Docetaxel; C552428:cabazitaxel; D012968:Etidronic Acid
keywords: additivity; chemotherapy; human cell lines; prostate carcinoma; radiosensitization; rhenium-188