99mTc tetrofosmin scintigraphy in acute leukaemia: the relationship between marrow uptake of tetrofosmin and P-glycoprotein and chemotherapy response.
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 99mTc 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 tetrofosmin was used in the investigation of acute leukaemia.


OBJECTIVE
To show the uptake pattern of 99mTc tetrofosmin in the bone marrow of patients with acute leukaemia, and to ascertain the relationship between 99mTc 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.


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 99mTc 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 99mTc 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 99mTc 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.


CONCLUSIONS
In this study, patients with acute leukaemia showed significant uptake of tetrofosmin into the bone marrow. The addition of basal and repeated 99mTc 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.
Sükan
Aysun
A
Department of Nuclear Medicine, Cukurova University Medical School, Adana, Turkey. aysunsukan@yahoo.com
Yapar
Zeynep
Z
SAhin
Berksoy
B
Kara
Oguz
O
Fuat Yapar
A
A
CEtiner
Salih
S
Kibar
Mustafa
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016896:Treatment Outcome; D019014:fas Receptor / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019014:fas Receptor; C078700:technetium tc-99m tetrofosmin