PMID- 19380450
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20211203
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 16
DP  - 2009 Jun 1
TI  - [18F]fluorodeoxyglucose positron emission tomography correlates with Akt pathway 
      activity but is not predictive of clinical outcome during mTOR inhibitor therapy.
PG  - 2697-704
LID - 10.1200/JCO.2008.18.8383 [doi]
AB  - PURPOSE: Positron emission tomography (PET) with [(18)F]fluorodeoxyglucose 
      (FDG-PET) has increasingly been used to evaluate the efficacy of anticancer 
      agents. We investigated the role of FDG-PET as a predictive marker for response 
      to mammalian target of rapamycin (mTOR) inhibition in advanced solid tumor 
      patients and in murine xenograft models. PATIENTS AND METHODS: Thirty-four 
      rapamycin-treated patients with assessable baseline and treatment FDG-PET and 
      computed tomography scans were analyzed from two clinical trials. Clinical 
      response was evaluated according to Response Evaluation Criteria in Solid Tumors, 
      and FDG-PET response was evaluated by quantitative changes and European 
      Organisation for Research and Treatment of Cancer (EORTC) criteria. Six murine 
      xenograft tumor models were treated with temsirolimus. Small animal FDG-PET scans 
      were performed at baseline and during treatment. The tumors were analyzed for the 
      expression of pAkt and GLUT1. RESULTS: Fifty percent of patients with increased 
      FDG-PET uptake and 46% with decreased uptake had progressive disease (PD). No 
      objective response was observed. By EORTC criteria, the sensitivity of 
      progressive metabolic disease on FDG-PET in predicting PD was 19%. Preclinical 
      studies demonstrated similar findings, and FDG-PET response correlated with pAkt 
      activation and plasma membrane GLUT1 expression. CONCLUSION: FDG-PET is not 
      predictive of proliferative response to mTOR inhibitor therapy in both clinical 
      and preclinical studies. Our findings suggest that mTOR inhibitors suppress the 
      formation of mTORC2 complex, resulting in the inhibition of Akt and glycolysis 
      independent of proliferation in a subset of tumors. Changes in FDG-PET may be a 
      pharmacodynamic marker for Akt activation during mTOR inhibitor therapy. FDG-PET 
      may be used to identify patients with persistent Akt activation following mTOR 
      inhibitor therapy.
FAU - Ma, Wen Wee
AU  - Ma WW
AD  - Roswell Park Cancer Institute, Buffalo, NY, USA.
FAU - Jacene, Heather
AU  - Jacene H
FAU - Song, Dongweon
AU  - Song D
FAU - Vilardell, Felip
AU  - Vilardell F
FAU - Messersmith, Wells A
AU  - Messersmith WA
FAU - Laheru, Dan
AU  - Laheru D
FAU - Wahl, Richard
AU  - Wahl R
FAU - Endres, Chris
AU  - Endres C
FAU - Jimeno, Antonio
AU  - Jimeno A
FAU - Pomper, Martin G
AU  - Pomper MG
FAU - Hidalgo, Manuel
AU  - Hidalgo M
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
GR  - R21 CA112919/CA/NCI NIH HHS/United States
GR  - U24 CA092871/CA/NCI NIH HHS/United States
GR  - U24 CA92871/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090420
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (SLC2A1 protein, human)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - J Clin Oncol. 2009 Jun 1;27(16):2580-2. PMID: 19380439
CIN - J Clin Oncol. 2010 May 20;28(15):e236-7; author reply e238. PMID: 20177016
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology/*therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Disease Progression
MH  - Female
MH  - *Fluorodeoxyglucose F18
MH  - Glucose Transporter Type 1/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms/*diagnostic imaging/*drug therapy/enzymology/pathology
MH  - Patient Selection
MH  - Phosphorylation
MH  - *Positron-Emission Tomography
MH  - Predictive Value of Tests
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Radiopharmaceuticals
MH  - Sirolimus/analogs & derivatives/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Tomography, X-Ray Computed
MH  - Treatment Outcome
MH  - Xenograft Model Antitumor Assays
PMC - PMC2689846
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2009/04/22 09:00
MHDA- 2009/06/12 09:00
PMCR- 2010/06/01
CRDT- 2009/04/22 09:00
PHST- 2009/04/22 09:00 [entrez]
PHST- 2009/04/22 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
PHST- 2010/06/01 00:00 [pmc-release]
AID - JCO.2008.18.8383 [pii]
AID - 88383 [pii]
AID - 10.1200/JCO.2008.18.8383 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Jun 1;27(16):2697-704. doi: 10.1200/JCO.2008.18.8383. Epub 
      2009 Apr 20.