Abstract | UNLABELLED: 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.
|
Authors | Rebecca A Dumont, MariaLuisa Tamma, Friederike Braun, Sandra Borkowski, Jean Claude Reubi, Helmut Maecke, Wolfgang A Weber, Rosalba Mansi |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 54
Issue 5
Pg. 762-9
(May 2013)
ISSN: 1535-5667 [Electronic] United States |
PMID | 23492884
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Oligopeptides
- Radioisotopes
- Receptors, Bombesin
- Lutetium
- Sirolimus
|
Topics |
- Animals
- Cell Line, Tumor
- Combined Modality Therapy
- Female
- Gene Expression Regulation, Neoplastic
(drug effects, radiation effects)
- Humans
- Lutetium
(therapeutic use)
- Male
- Mice
- Molecular Targeted Therapy
(methods)
- Oligopeptides
(chemistry, pharmacokinetics, pharmacology, therapeutic use)
- Prostatic Neoplasms
(drug therapy, pathology, radiotherapy)
- Radioisotopes
(therapeutic use)
- Receptors, Bombesin
(antagonists & inhibitors, metabolism)
- Sirolimus
(pharmacology, therapeutic use)
|