99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice.
OBJECTIVE
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 x 10(6) 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.


CONCLUSIONS
MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mTc glucarate can potentially localize drug resistant breast tumours.
Liu
Zhonglin
Z
Department of Radiology, The University of Arizona, Tucson, 85724-5067, USA. zliu@radiology.arizona.edu
Stevenson
Gail D
GD
Barrett
Harrison H
HH
Kastis
George A
GA
Bettan
Michel
M
Furenlid
Lars R
LR
Wilson
Donald W
DW
Woolfenden
James M
JM
Pak
Koon Yan
KY
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005240:Feasibility Studies; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014183:Transplantation, Heterologous
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi; D005937:Glucaric Acid