99mTc-MIBI scintigraphy as an indicator of the chemosensitivity of anthracyclines in patients with breast cancer.
BACKGROUND
Chemoresistance of tumor cells is involved with many factors, one of which is the P-glycoprotein function to pump anthracyclines out of cells. 99mTc-MIBI accumulates in several tumors, and some of these cells wash out 99mTc-MIBI through P-glycoprotein.


METHODS
We investigated if the wash-out of 99mTc-MIBI from the tumor in fifteen female patients with breast cancer could be related with the chemosensitivity of anticancer agents; doxorubicin (DOX), epirubicin (FAM), pinorubicin (PINO), mitomycin (MMC), cisplatin (CDDP), and 5-fluorouracil (5-FU), in each tumor tissues. The wash-out of 99mTc-MIBI, defined as retention index, was quantified from an early and delayed 99mTc-MIBI imaging. The chemosensitivity of the anticancer agent, and inhibition ratio, was determined in vitro assay by using surgical specimens obtained from patients who underwent 99mTc-MIBI imaging. P-glycoprotein in the surgical specimen was studied by immunohistochemical staining on its paraffin section using a monoclonal antibody.


RESULTS
Inhibition ratio of anthracycline agent, DOX, FAM or PINO, was well correlated with retention index of 99mTc-MIBI with coefficient of 0.75, 0.60, or 0.62, respectively, whereas a poor relationship was observed for MMC and CDDP. The retention indices of 99mTc-MIBI were remarkably small for patients in the P-glycoprotein positive group.


CONCLUSIONS
99mTc-MIBI retention index quantified from its early and delayed scintigraphy is a good indicator to predict the chemosensitivity of anthracyclines in untreated breast cancer.
Fujii
H
H
Department of Radiology, Keio University School of Medicine, Tokyo, Japan.
Nakamura
K
K
Kubo
A
A
Enomoto
K
K
Ikeda
T
T
Kubota
T
T
Matsuzaki
S W
SW
Kitajima
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D015251:Epirubicin / Q000633:toxicity; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D008875:Middle Aged; D008937:Mitomycins / Q000633:toxicity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012044:Regression Analysis; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018943:Anthracyclines; D008937:Mitomycins; D019275:Radiopharmaceuticals; D015251:Epirubicin; D004317:Doxorubicin; D017256:Technetium Tc 99m Sestamibi; D002945:Cisplatin; D005472:Fluorouracil