Fractional retention of technetium-99m-sestamibi as an index of P- glycoprotein expression in untreated breast cancer patients

Silvana Del Vecchio, Andrea Ciarmiello, Leonardo Pace, Maria I. Potena, Maria V. Carriero, Ciro Mainolfi, Renato Thomas, Giuseppe D'Aiuto, Takashi Tsuruo, Marco Salvatore

Research output: Contribution to journalArticle

Abstract

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 (99m)Tc-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 (99m)Tc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of (99m)Tc-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 (99m)Tc-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) (13 <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 0.55 and 0.25 in low- and high-Pgp-expressing tumors, respectively. Conclusion: The determination of fractional retention of (99m)Tc-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.

Original languageEnglish
Pages (from-to)1348-1351
Number of pages4
JournalJournal of Nuclear Medicine
Volume38
Issue number9
Publication statusPublished - Sep 1997

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Technetium Tc 99m Sestamibi
P-Glycoprotein
Breast Neoplasms
Neoplasms
Multiple Drug Resistance
Autoradiography
Breast
Monoclonal Antibodies
Phenotype
Sensitivity and Specificity

Keywords

  • Breast carcinoma
  • Multidrug resistance
  • P-glycoprotein
  • Technetium-99m-sestamibi

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Fractional retention of technetium-99m-sestamibi as an index of P- glycoprotein expression in untreated breast cancer patients. / Del Vecchio, Silvana; Ciarmiello, Andrea; Pace, Leonardo; Potena, Maria I.; Carriero, Maria V.; Mainolfi, Ciro; Thomas, Renato; D'Aiuto, Giuseppe; Tsuruo, Takashi; Salvatore, Marco.

In: Journal of Nuclear Medicine, Vol. 38, No. 9, 09.1997, p. 1348-1351.

Research output: Contribution to journalArticle

Del Vecchio, S, Ciarmiello, A, Pace, L, Potena, MI, Carriero, MV, Mainolfi, C, Thomas, R, D'Aiuto, G, Tsuruo, T & Salvatore, M 1997, 'Fractional retention of technetium-99m-sestamibi as an index of P- glycoprotein expression in untreated breast cancer patients', Journal of Nuclear Medicine, vol. 38, no. 9, pp. 1348-1351.
Del Vecchio, Silvana ; Ciarmiello, Andrea ; Pace, Leonardo ; Potena, Maria I. ; Carriero, Maria V. ; Mainolfi, Ciro ; Thomas, Renato ; D'Aiuto, Giuseppe ; Tsuruo, Takashi ; Salvatore, Marco. / Fractional retention of technetium-99m-sestamibi as an index of P- glycoprotein expression in untreated breast cancer patients. In: Journal of Nuclear Medicine. 1997 ; Vol. 38, No. 9. pp. 1348-1351.
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abstract = "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 (99m)Tc-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 (99m)Tc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of (99m)Tc-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 (99m)Tc-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) (13 <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 0.55 and 0.25 in low- and high-Pgp-expressing tumors, respectively. Conclusion: The determination of fractional retention of (99m)Tc-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.",
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T1 - Fractional retention of technetium-99m-sestamibi as an index of P- glycoprotein expression in untreated breast cancer patients

AU - Del Vecchio, Silvana

AU - Ciarmiello, Andrea

AU - Pace, Leonardo

AU - Potena, Maria I.

AU - Carriero, Maria V.

AU - Mainolfi, Ciro

AU - Thomas, Renato

AU - D'Aiuto, Giuseppe

AU - Tsuruo, Takashi

AU - Salvatore, Marco

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N2 - 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 (99m)Tc-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 (99m)Tc-sestamibi, and static planar images of the breast were obtained at 10, 60 and 240 min. The fractional retention of (99m)Tc-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 (99m)Tc-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) (13 <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 0.55 and 0.25 in low- and high-Pgp-expressing tumors, respectively. Conclusion: The determination of fractional retention of (99m)Tc-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.

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