Fractional retention of technetium-99m-sestamibi as an index of P-glycoprotein expression in untreated breast cancer patients.
The multidrug-resistant phenotype is characterized by the reduced intracellular retention of several structurally and functionally unrelated cytotoxic compounds due to the energy-dependent pump activity of P-glycoprotein (Pgp). Because 99mTc-sestamibi is a suitable transport substrate of Pgp, we tested whether the time-dependent fractional retention of this tracer could be used as an index of Pgp expression in untreated breast carcinomas.


METHODS
Twenty-seven patients with histologically confirmed breast carcinoma were intravenously injected with 740 MBq (20 mCi) of 99mTc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of 99mTc-sestamibi was then calculated as the ratios between 60 and 10 min (R60/10) and between 240 and 10 min (R240/10) of decay-corrected counts/pixel registered in the region of interest drawn around the tumor. Surgically excised tumors were then obtained from each patient, and Pgp levels were determined using 125I-labeled MRK16 monoclonal antibody and in vitro quantitative autoradiography.


RESULTS
The fractional retention of 99mTc-sestamibi at 60 and 240 min was significantly higher in tumors with low Pgp levels (Group I, n = 18) as compared to that measured in tumors with high Pgp expression (Group II, n = 9) (p < 0.001). In particular, R60/10 values were 0.86 and 0.59 in breast carcinomas of Groups I and II, respectively, whereas the values of R240/10 were 0.56 and 0.25 in low- and high-Pgp-expressing tumors, respectively.


CONCLUSIONS
The determination of fractional retention of 99mTc-sestamibi may be used as a simple functional test for Pgp expression in untreated breast cancer. A preliminary estimate of the sensitivity and the specificity of the test indicates its potential use in clinical practice to identify patients with a high probability of developing multidrug resistance.
Del Vecchio
S
S
Cattedra di Medicina Nucleare, Università Federico II, Centro per lo Studio della Medicina Nucleare CNR, Naples, Italy.
Ciarmiello
A
A
Pace
L
L
Potena
M I
MI
Carriero
M V
MV
Mainolfi
C
C
Thomas
R
R
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 / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009363:Neoplasm Proteins / Q000032:analysis*; D011877:Radionuclide Imaging; D012307:Risk Factors; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins; D017256:Technetium Tc 99m Sestamibi