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In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients

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Abstract

Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of99mTc-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 after99mTc-sestamibi scan and Pgp levels were determined using125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of99mTc-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 with99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.

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Authors and Affiliations

  1. Medicina Nucleare, Istituto di Scienze Radiologiche II Facoltá di Medicina, Universitá degli Studi “Federico II”, Via Pansini, 5, I-80131, Naples, Italy

    Silvana Del Vecchio, Ciro Mainolfi & Marco Salvatore

  2. Istituto Nazionale per lo Studio e la Cura dei tumori, Via M. Semmola, Naples, Italy

    Andrea Ciarmiello, Maria I. Potena, Maria V. Carriero, Gerardo Botti, Renato Thomas, Maria Cerra & Giuseppe D'Aiuto

  3. Institute of Applied Microbiology, University of Tokyo, Bunkyo-Ku, 113, Tokyo, Japan

    Takashi Tsuruo

  4. Centro per lo Studio della Medicina Nucleare CNR, Via Pansini, 5, Naples, Italy

    Silvana Del Vecchio, Ciro Mainolfi & Marco Salvatore

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  1. Silvana Del Vecchio
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  2. Andrea Ciarmiello
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Del Vecchio, S., Ciarmiello, A., Potena, M.I. et al. In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients. Eur J Nucl Med 24, 150–159 (1997). https://doi.org/10.1007/BF02439547

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  • DOI: https://doi.org/10.1007/BF02439547

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