Prediction of chemotherapeutic response by Technetium 99m--MIBI scintigraphy in breast carcinoma patients.
BACKGROUND
Significance of Technetium 99m ((99m)Tc)-MIBI scintigraphy in the prediction of response to anthracylines and taxanes (both are substrates for P-glycoprotein [P-gp]) as well as relation between (99m)Tc-MIBI uptake and P-gp or MDR1 mRNA expression in tumors were studied in patients with breast carcinoma.


METHODS
Forty-six female patients with locally advanced (n = 15) or metastatic (n = 31) breast carcinoma were recruited in this study. Before chemotherapy (epirubicin and cyclophosphamide [n = 20] or decetaxel [n = 26]), (99m)Tc-MIBI scintigraphy was performed to obtain the T/N (tumor to normal tissue) ratios of (99m)Tc-MIBI uptake at 10 minutes (T/N[e]) and at 180 minutes (T/N[d]) after the (99m)Tc-MIBI injection. Expression of MDR1 mRNA and P-gp in tumors (n = 32) were determined by a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively.


RESULTS
Clinical significance of T/N(e) and T/N(d) ratios in the prediction of chemotherapeutic response was evaluated using the arbitrary cutoff values of 3.0 for T/N(e) ratios and 2.0 for T/N(d) ratios. Positive predictive value, negative predictive value, and diagnostic accuracy of T/N(d) ratios (81.0%, 96.0%, and 89.1%, respectively) were higher, although statistically not significant, than those of T/N(e) ratios (73.3%, 77.4%, and 76.1%, respectively), and these values were not affected by type of chemotherapy. MDR1 mRNA levels were not significantly different between the lesions with high (> or = 2.0) and low (< 2.0) T/N(d) ratios, but P-gp expression was significantly (P < 0.01) higher in the lesions with low T/N(d) ratios than in those with high T/N(d) ratios.


CONCLUSIONS
T/N(d) ratios determined by (99m)Tc-MIBI scintigraphy are useful in the prediction of response to chemotherapy with epirubicin and cyclophosphamide or docetaxel as well as in the in vivo evaluation of P-gp expression status in tumors in patients with locally advanced or recurrent breast carcinoma.
Takamura
Y
Y
Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
Miyoshi
Y
Y
Taguchi
T
T
Noguchi
S
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000188:drug therapy; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043823:Taxoids; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D016896:Treatment Outcome
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D001952:Bridged-Ring Compounds; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D043823:Taxoids; C080625:taxane; D017256:Technetium Tc 99m Sestamibi