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WOS: 000223478200004 PubMed ID: 15266171 Background The non-invasive detection of P-glycoprotein (Pgp) and multidrug resistance related proteins in vivo, will represent the greatest challenge in overcoming multidrug resistance. Although Tc-99m tetrofosmin has been used previously as a myocardial perfusion agent, it is now also being used in the imaging of various tumours. In the current study, Tc-99m tetrofosmin was used in the investigation of acute leukaemia. Aim To show the uptake pattern of Tc-99m tetrofosmin in the bone marrow of patients with acute leukaemia, and to ascertain the relationship between Tc-99m tetrofosmin uptake and the level of Pgp expression and their relation to the response to chemotherapy. In addition, CD95, which is an indicator of apoptosis (programmed cell death), has also been assessed. Materials and methods Pgp and CD95 were detected by using flow cytometry. Of the 27 acute leukaemia patients assessed, nine had previously received chemotherapy, and 18 had had an initial diagnosis. All patients had undergone Tc-99m tetrofosmin scintigraphy, and their Pgp and CD95 levels had been determined. The same parameters were studied again for 14 patients. The responses to chemotherapy were assessed by patients' clinicians. A control group of 37 patients without bone marrow pathology was also studied in order to provide comparisons for the scintigraphy results. The control images were assessed only qualitatively. Results In leukaemia patients the uptake of Tc-99m tetrofosmin into bone marrow was found to be considerably higher than in control patients (P = 0.000). An analysis of the relationship between Pgp, CD95, and the qualitative and quantitative tetrofosmin uptake ratios (URs) showed that there was an inverse correlation only between Pgp and the quantitative uptake ratio (P = 0.016, r = -0.461). When the patients were grouped as 'good' and 'poor', as related to the chemotherapy response, there were no meaningful differences between these two groups regarding Pgp, CD95 and tetrofosmin URs (P > 0.05). By evaluating the scintigraphic findings of the 'repeated' 14 patients, we showed that if the Tc-99m tetrofosmin UR in the second imaging test was reduced by > 0.08, the response to chemotherapy tended to be good. This method, based on follow-up scanning with tetrofosmin, showed a sensitivity of 83% and a specificity of 62% in the prediction of a 'good' response, if a decrease of 0.08 was taken into consideration. Conclusion In this study, patients with acute leukaemia showed significant uptake of tetrofosmin into the bone marrow. The addition of basal and repeated Tc-99m tetrofosmin scintigraphy to the management protocol for leukaemia could lead to the preferential determination of responses to chemotherapy, by evaluating whole bone marrow non-invasively. This method seems promising, but it needs further support from various similar investigations comprising more patients in order to confirm our results. (C) 2004 Lippincott Williams Wilkins. |
