Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Zhonglin Liu, Gail D. Stevenson, Harrison H Barrett, Lars R Furenlid, Donald W. Wilson, George A. Kastis, Michael Bettan, James M. Woolfenden

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: 99mTc-sestamibi (MIBI) and 99mTc- tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. Methods: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. Results: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62±0.15 vs. 0.55±0.05, P<.05) for TF and 1.9-fold (1.21±0.04 vs. 0.64±0.05, P<.05) for MIBI but did not affect MCF7/WT. Conclusions: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

Original languageEnglish (US)
Pages (from-to)573-583
Number of pages11
JournalNuclear Medicine and Biology
Volume32
Issue number6
DOIs
StatePublished - Aug 2005

Fingerprint

Technetium Tc 99m Sestamibi
Multiple Drug Resistance
Heterografts
Breast Neoplasms
P-Glycoprotein
Single-Photon Emission-Computed Tomography
SCID Mice
technetium Tc 99m 1,2-bis(bis(2-ethoxyethyl)phosphino)ethane
valspodar
Intravenous Injections
Pharmaceutical Preparations

Keywords

  • Tc-sestamibi
  • Tc-tetrofosmin
  • Human breast cancer
  • Multidrug resistance
  • P-glycoprotein modulation
  • SPECT

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin. / Liu, Zhonglin; Stevenson, Gail D.; Barrett, Harrison H; Furenlid, Lars R; Wilson, Donald W.; Kastis, George A.; Bettan, Michael; Woolfenden, James M.

In: Nuclear Medicine and Biology, Vol. 32, No. 6, 08.2005, p. 573-583.

Research output: Contribution to journalArticle

Liu, Zhonglin ; Stevenson, Gail D. ; Barrett, Harrison H ; Furenlid, Lars R ; Wilson, Donald W. ; Kastis, George A. ; Bettan, Michael ; Woolfenden, James M. / Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin. In: Nuclear Medicine and Biology. 2005 ; Vol. 32, No. 6. pp. 573-583.
@article{0f45c7cc5b3f4f0280d2b870a617a02d,
title = "Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin",
abstract = "Background: 99mTc-sestamibi (MIBI) and 99mTc- tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. Methods: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. Results: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation ({\%}ID/g) in MCF7/AdrR 3.0-fold (1.62±0.15 vs. 0.55±0.05, P<.05) for TF and 1.9-fold (1.21±0.04 vs. 0.64±0.05, P<.05) for MIBI but did not affect MCF7/WT. Conclusions: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.",
keywords = "Tc-sestamibi, Tc-tetrofosmin, Human breast cancer, Multidrug resistance, P-glycoprotein modulation, SPECT",
author = "Zhonglin Liu and Stevenson, {Gail D.} and Barrett, {Harrison H} and Furenlid, {Lars R} and Wilson, {Donald W.} and Kastis, {George A.} and Michael Bettan and Woolfenden, {James M.}",
year = "2005",
month = "8",
doi = "10.1016/j.nucmedbio.2005.04.014",
language = "English (US)",
volume = "32",
pages = "573--583",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

AU - Liu, Zhonglin

AU - Stevenson, Gail D.

AU - Barrett, Harrison H

AU - Furenlid, Lars R

AU - Wilson, Donald W.

AU - Kastis, George A.

AU - Bettan, Michael

AU - Woolfenden, James M.

PY - 2005/8

Y1 - 2005/8

N2 - Background: 99mTc-sestamibi (MIBI) and 99mTc- tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. Methods: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. Results: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62±0.15 vs. 0.55±0.05, P<.05) for TF and 1.9-fold (1.21±0.04 vs. 0.64±0.05, P<.05) for MIBI but did not affect MCF7/WT. Conclusions: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

AB - Background: 99mTc-sestamibi (MIBI) and 99mTc- tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. Methods: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. Results: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62±0.15 vs. 0.55±0.05, P<.05) for TF and 1.9-fold (1.21±0.04 vs. 0.64±0.05, P<.05) for MIBI but did not affect MCF7/WT. Conclusions: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

KW - Tc-sestamibi

KW - Tc-tetrofosmin

KW - Human breast cancer

KW - Multidrug resistance

KW - P-glycoprotein modulation

KW - SPECT

UR - http://www.scopus.com/inward/record.url?scp=22144484811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22144484811&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2005.04.014

DO - 10.1016/j.nucmedbio.2005.04.014

M3 - Article

C2 - 16026704

AN - SCOPUS:22144484811

VL - 32

SP - 573

EP - 583

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 6

ER -