In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients.
Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether 99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of 99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of 99mTc-sestamibi and underwent a 15-min dynamic study followed by the acquisition of static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after 99mTc-sestamibi scan and Pgp levels were determined using 125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of 99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of 99mTc-sestamibi, calculated from decay-corrected time-activity curves, ranged between 0.00121 and 0.01690 min-1 and were directly correlated with Pgp levels measured in the same tumours (r=0.62; P<0.001). Ten out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast lesions and showed a mean concentration of 5.73+/- 1.63 pmol/g of tumour (group A). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29+/-0.64 pmol/g (group B), equivalent to that found in benign breast lesions. 99mTc-sestamibi efflux from tumours of group A was 2.7 times higher than that observed in tumours of group B (0.00686+/-0.00390 min-1 vs 0.00250+/-0.00090 min-1, P<0.001). The in vivo functional test with 99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of 99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.
Vecchio
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SD
Medicina Nucleare, Istituto di Scienze Radiologiche, Universitá degli Studi "Federico II", Via Pansini, 5, Naples, Italy.
Ciarmiello
A
A
Potena
M I
MI
Carriero
M V
MV
Mainolfi
C
C
Botti
G
G
Thomas
R
R
Cerra
M
M
D'Aiuto
G
G
Tsuruo
T
T
Salvatore
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D001345:Autoradiography; D001943:Breast Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000000981:diagnostic imaging; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000000981:diagnostic imaging; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D010641:Phenotype; D011877:Radionuclide Imaging; D012680:Sensitivity and Specificity; D017256:Technetium Tc 99m Sestamibi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017256:Technetium Tc 99m Sestamibi