[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: Correlation of hypoxia, metabolism and VEGF expression

J. G. Rajendran, D. C. Wilson, E. U. Conrad, L. M. Peterson, J. D. Bruckner, J. S. Rasey, L. K. Chin, P. D. Hofstrand, J. R. Grierson, J. F. Eary, K. A. Krohn

Research output: Research - peer-reviewArticle

  • 170 Citations

Abstract

Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [18F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio (≥1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09-0.79) pretreatment and 0.32 (range -0.46-0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship between the hypoxic volume and the tumor volume or VEGF expression. Identification of hypoxia and development of a more complete biologic profile of STS will serve to guide more rational, individualized cancer treatment approaches.

LanguageEnglish (US)
Pages695-704
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume30
Issue number5
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Fluorodeoxyglucose F18
Sarcoma
Positron-Emission Tomography
Vascular Endothelial Growth Factor A
fluoromisonidazole
Hypoxia
Neoplasms
Therapeutics
Tumor Burden
Drug Therapy
Adjuvant Chemotherapy
Fluorine
Energy Metabolism
Radiotherapy
Glucose

Keywords

  • FDG
  • FMISO
  • Hypoxia
  • Soft tissue sarcomas
  • VEGF

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas : Correlation of hypoxia, metabolism and VEGF expression. / Rajendran, J. G.; Wilson, D. C.; Conrad, E. U.; Peterson, L. M.; Bruckner, J. D.; Rasey, J. S.; Chin, L. K.; Hofstrand, P. D.; Grierson, J. R.; Eary, J. F.; Krohn, K. A.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 30, No. 5, 01.05.2003, p. 695-704.

Research output: Research - peer-reviewArticle

Rajendran, JG, Wilson, DC, Conrad, EU, Peterson, LM, Bruckner, JD, Rasey, JS, Chin, LK, Hofstrand, PD, Grierson, JR, Eary, JF & Krohn, KA 2003, '[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: Correlation of hypoxia, metabolism and VEGF expression' European Journal of Nuclear Medicine and Molecular Imaging, vol 30, no. 5, pp. 695-704.
Rajendran, J. G. ; Wilson, D. C. ; Conrad, E. U. ; Peterson, L. M. ; Bruckner, J. D. ; Rasey, J. S. ; Chin, L. K. ; Hofstrand, P. D. ; Grierson, J. R. ; Eary, J. F. ; Krohn, K. A./ [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas : Correlation of hypoxia, metabolism and VEGF expression. In: European Journal of Nuclear Medicine and Molecular Imaging. 2003 ; Vol. 30, No. 5. pp. 695-704
@article{16c4200d307d400fb685a5c604e4d1fe,
title = "[18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: Correlation of hypoxia, metabolism and VEGF expression",
abstract = "Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [18F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio (≥1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09-0.79) pretreatment and 0.32 (range -0.46-0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship between the hypoxic volume and the tumor volume or VEGF expression. Identification of hypoxia and development of a more complete biologic profile of STS will serve to guide more rational, individualized cancer treatment approaches.",
keywords = "FDG, FMISO, Hypoxia, Soft tissue sarcomas, VEGF",
author = "Rajendran, {J. G.} and Wilson, {D. C.} and Conrad, {E. U.} and Peterson, {L. M.} and Bruckner, {J. D.} and Rasey, {J. S.} and Chin, {L. K.} and Hofstrand, {P. D.} and Grierson, {J. R.} and Eary, {J. F.} and Krohn, {K. A.}",
year = "2003",
month = "5",
volume = "30",
pages = "695--704",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas

T2 - European Journal of Nuclear Medicine and Molecular Imaging

AU - Rajendran,J. G.

AU - Wilson,D. C.

AU - Conrad,E. U.

AU - Peterson,L. M.

AU - Bruckner,J. D.

AU - Rasey,J. S.

AU - Chin,L. K.

AU - Hofstrand,P. D.

AU - Grierson,J. R.

AU - Eary,J. F.

AU - Krohn,K. A.

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [18F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio (≥1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09-0.79) pretreatment and 0.32 (range -0.46-0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship between the hypoxic volume and the tumor volume or VEGF expression. Identification of hypoxia and development of a more complete biologic profile of STS will serve to guide more rational, individualized cancer treatment approaches.

AB - Hypoxia imparts resistance to radiotherapy and chemotherapy and also promotes a variety of changes in tumor biology through inducible promoters. The purpose of this study was to evaluate the use of positron emission tomography (PET) imaging with fluorine-18 fluoromisonidazole (FMISO) in soft tissue sarcomas (STS) as a measure of hypoxia and to compare the results with those obtained using [18F]fluorodeoxyglucose (FDG) and other known biologic correlates. FDG evaluates energy metabolism in tumors while FMISO uptake is proportional to tissue hypoxia. FMISO uptake was compared with FDG uptake. Vascular endothelial growth factor (VEGF) expression was also compared with FMISO uptake. Nineteen patients with STS underwent PET scanning with quantitative determination of FMISO and FDG uptake prior to therapy (neo-adjuvant chemotherapy or surgery alone). Ten patients receiving neo-adjuvant chemotherapy were also imaged after chemotherapy but prior to surgical resection. Standardized uptake value (SUV) was used to describe FDG uptake; regional tissue to blood ratio (≥1.2 was considered significant) was used for FMISO uptake. Significant hypoxia was found in 76% of tumors imaged prior to therapy. No correlation was identified between pretherapy hypoxic volume (HV) and tumor grade (r=0.15) or tumor volume (r=0.03). The correlation of HV with VEGF expression was 0.39. Individual tumors showed marked heterogeneity in regional VEGF expression. The mean pixel-by-pixel correlation between FMISO and FDG uptake was 0.49 (range 0.09-0.79) pretreatment and 0.32 (range -0.46-0.72) after treatment. Most tumors showed evidence of reduced uptake of both FMISO and FDG following chemotherapy. FMISO PET demonstrates areas of significant and heterogeneous hypoxia in soft tissue sarcomas. The significant discrepancy between FDG and FMISO uptake seen in this study indicates that regional hypoxia and glucose metabolism do not always correlate. Similarly, we did not find any relationship between the hypoxic volume and the tumor volume or VEGF expression. Identification of hypoxia and development of a more complete biologic profile of STS will serve to guide more rational, individualized cancer treatment approaches.

KW - FDG

KW - FMISO

KW - Hypoxia

KW - Soft tissue sarcomas

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=12444290525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12444290525&partnerID=8YFLogxK

M3 - Article

VL - 30

SP - 695

EP - 704

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 5

ER -