TY - JOUR
T1 - Combination 186Re-HEDP and cisplatin supra-additive treatment effects in prostate cancer cells
AU - Geldof, Albert A.
AU - De Rooij, Laurens
AU - Versteegh, Richard T.
AU - Newling, Donald W.W.
AU - Teule, Gerrit J.J.
PY - 1999/4/1
Y1 - 1999/4/1
N2 - Radionuclide therapy has proven to be an efficacious palliative treatment for metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. Methods: This study explores the radiosensitizing properties of cisplatin when combined with 186Re-labeled hydroxyethylidene diphosphonate (HEDP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant incubation during 4 d, combining various concentrations of cisplatin (0, 0.42, 0.83 and 1.67μmol/L) and 186Re- HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100 μCi/mL, respectively]) was followed by the determination of the cell numbers surviving and the replating of these cells in semisolid agar. Results: The surviving fraction of clonogenic tumor cells after combination treatment clearly showed synergism when analyzed by a panel of three different published analytical methods. In addition, analysis of variance demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with 186Re-HEDP and cisplatin by sequential incubation yielded similar, but never superior results. Conclusion: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in metastatic prostate cancer in a more than additive way.
AB - Radionuclide therapy has proven to be an efficacious palliative treatment for metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. Methods: This study explores the radiosensitizing properties of cisplatin when combined with 186Re-labeled hydroxyethylidene diphosphonate (HEDP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant incubation during 4 d, combining various concentrations of cisplatin (0, 0.42, 0.83 and 1.67μmol/L) and 186Re- HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100 μCi/mL, respectively]) was followed by the determination of the cell numbers surviving and the replating of these cells in semisolid agar. Results: The surviving fraction of clonogenic tumor cells after combination treatment clearly showed synergism when analyzed by a panel of three different published analytical methods. In addition, analysis of variance demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with 186Re-HEDP and cisplatin by sequential incubation yielded similar, but never superior results. Conclusion: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in metastatic prostate cancer in a more than additive way.
KW - Re- hydroxyethylidene diphosphonate
KW - Combination therapy
KW - In vitro
KW - Prostate cancer
KW - Synergism
UR - http://www.scopus.com/inward/record.url?scp=0032588564&partnerID=8YFLogxK
M3 - Article
C2 - 10210227
AN - SCOPUS:0032588564
VL - 40
SP - 667
EP - 671
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 4
ER -