99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice

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

Research output: Contribution to journalArticle

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Abstract

Background and aim: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. Methods: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 × 106 cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. Results: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. Conclusion: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mT glucarate can potentially localize drug resistant breast tumours.

Original languageEnglish (US)
Pages (from-to)711-720
Number of pages10
JournalNuclear Medicine Communications
Volume25
Issue number7
DOIs
StatePublished - Jul 2004

Fingerprint

SCID Mice
Heterografts
Breast Neoplasms
Pharmaceutical Preparations
Neoplasms
MCF-7 Cells
Multiple Drug Resistance
Single-Photon Emission-Computed Tomography
Technetium Tc 99m Sestamibi
technetium Tc 99m glucarate
Injections
P-Glycoprotein
Thigh
Intravenous Injections
Doxorubicin
Western Blotting
Cell Line

Keywords

  • Tc glucarate
  • Tc sestamibi
  • Breast cancer
  • High-resolution SPECT
  • Multidrug resistant
  • SCID mice

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice. / Liu, Zhonglin; Stevenson, Gail D.; Barrett, Harrison H; Kastis, George A.; Bettan, Michel; Furenlid, Lars R; Wilson, Donald W.; Woolfenden, James M.; Koon, Yan Pak.

In: Nuclear Medicine Communications, Vol. 25, No. 7, 07.2004, p. 711-720.

Research output: Contribution to journalArticle

Liu, Zhonglin ; Stevenson, Gail D. ; Barrett, Harrison H ; Kastis, George A. ; Bettan, Michel ; Furenlid, Lars R ; Wilson, Donald W. ; Woolfenden, James M. ; Koon, Yan Pak. / 99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice. In: Nuclear Medicine Communications. 2004 ; Vol. 25, No. 7. pp. 711-720.
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abstract = "Background and aim: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. Methods: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 × 106 cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. Results: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation ({\%}ID/g) compared to MIBI. Conclusion: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mT glucarate can potentially localize drug resistant breast tumours.",
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author = "Zhonglin Liu and Stevenson, {Gail D.} and Barrett, {Harrison H} and Kastis, {George A.} and Michel Bettan and Furenlid, {Lars R} and Wilson, {Donald W.} and Woolfenden, {James M.} and Koon, {Yan Pak}",
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T1 - 99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice

AU - Liu, Zhonglin

AU - Stevenson, Gail D.

AU - Barrett, Harrison H

AU - Kastis, George A.

AU - Bettan, Michel

AU - Furenlid, Lars R

AU - Wilson, Donald W.

AU - Woolfenden, James M.

AU - Koon, Yan Pak

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N2 - Background and aim: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. Methods: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 × 106 cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. Results: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. Conclusion: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mT glucarate can potentially localize drug resistant breast tumours.

AB - Background and aim: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. Methods: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 × 106 cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. Results: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. Conclusion: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mT glucarate can potentially localize drug resistant breast tumours.

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