PMID- 23492884
OWN - NLM
STAT- MEDLINE
DCOM- 20130904
LR  - 20131121
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Linking)
VI  - 54
IP  - 5
DP  - 2013 May
TI  - Targeted radiotherapy of prostate cancer with a gastrin-releasing peptide 
      receptor antagonist is effective as monotherapy and in combination with 
      rapamycin.
PG  - 762-9
LID - 10.2967/jnumed.112.112169 [doi]
AB  - The gastrin-releasing peptide receptor (GRPr) is overexpressed in prostate cancer 
      and is an attractive target for radionuclide therapy. In addition, inhibition of 
      the protein kinase mammalian target of rapamycin (mTOR) has been shown to 
      sensitize various cancer cells to the effects of radiotherapy. METHODS: To 
      determine the effect of treatment with rapamycin and radiotherapy with a novel 
      (177)Lu-labeled GRPr antagonist ((177)Lu-RM2, BAY 1017858) alone and in 
      combination, in vitro and in vivo studies were performed using the human PC-3 
      prostate cancer cell line. PC-3 cell proliferation and (177)Lu-RM2 uptake after 
      treatment with rapamycin were assessed in vitro. To determine the influence of 
      rapamycin on (177)Lu-RM2 tumor uptake, in vivo small-animal PET studies with 
      (68)Ga-RM2 were performed after treatment with rapamycin. To study the efficacy 
      of (177)Lu-RM2 in vivo, mice with subcutaneous PC-3 tumors were treated with 
      (177)Lu-RM2 alone or after pretreatment with rapamycin. RESULTS: Stable 
      expression of GRPr was maintained after rapamycin treatment with doses up to 4 
      mg/kg in vivo. Monotherapy with (177)Lu-RM2 at higher doses (72 and 144 MBq) was 
      effective in inducing complete tumor remission in 60% of treated mice. Treatment 
      with 37 MBq of (177)Lu-RM2 and rapamycin in combination led to significantly 
      longer survival than with either agent alone. No treatment-related toxicity was 
      observed. CONCLUSION: Radiotherapy using a (177)Lu-labeled GRPr antagonist alone 
      or in combination with rapamycin was efficacious in inhibiting in vivo tumor 
      growth and may be a promising strategy for treatment of prostate cancer.
FAU - Dumont, Rebecca A
AU  - Dumont RA
AD  - Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany. 
      rdumont@ucla.edu
FAU - Tamma, MariaLuisa
AU  - Tamma M
FAU - Braun, Friederike
AU  - Braun F
FAU - Borkowski, Sandra
AU  - Borkowski S
FAU - Reubi, Jean Claude
AU  - Reubi JC
FAU - Maecke, Helmut
AU  - Maecke H
FAU - Weber, Wolfgang A
AU  - Weber WA
FAU - Mansi, Rosalba
AU  - Mansi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130314
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Oligopeptides)
RN  - 0 (Radioisotopes)
RN  - 0 (Receptors, Bombesin)
RN  - 5H0DOZ21UJ (Lutetium)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Combined Modality Therapy
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects/radiation effects
MH  - Humans
MH  - Lutetium/therapeutic use
MH  - Male
MH  - Mice
MH  - Molecular Targeted Therapy/*methods
MH  - Oligopeptides/chemistry/pharmacokinetics/pharmacology/*therapeutic use
MH  - Prostatic Neoplasms/*drug therapy/pathology/*radiotherapy
MH  - Radioisotopes/therapeutic use
MH  - Receptors, Bombesin/*antagonists & inhibitors/metabolism
MH  - Sirolimus/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - bombesin antagonist
OT  - combination therapy
OT  - prostate cancer
OT  - radiopeptide therapy
EDAT- 2013/03/16 06:00
MHDA- 2013/09/05 06:00
CRDT- 2013/03/16 06:00
PHST- 2013/03/16 06:00 [entrez]
PHST- 2013/03/16 06:00 [pubmed]
PHST- 2013/09/05 06:00 [medline]
AID - jnumed.112.112169 [pii]
AID - 10.2967/jnumed.112.112169 [doi]
PST - ppublish
SO  - J Nucl Med. 2013 May;54(5):762-9. doi: 10.2967/jnumed.112.112169. Epub 2013 Mar 
      14.