99mTc-MIBI SPET in non-small cell lung cancer in relationship with Pgp and prognosis

Abstract

Higher technetium-99m methoxyisobutylisonitrile (MIBI) uptake in non-small cell lung cancer (NSCLC) has been reported to be associated with a positive response to chemotherapy. It has previously been found that in tumour cells, P-glycoprotein (Pgp) expression is of importance for tracer uptake. However, some studies have indicated that Pgp expression does not play an important role in (99m)Tc-MIBI uptake in NSCLC; indeed, a negative correlation between (99m)Tc-MIBI uptake and Pgp expression has been reported. Against the background of conflicting results, our aim was to evaluate the relationship between (99m)Tc-MIBI uptake, prognosis and Pgp expression in NSCLC. A total of 37 patients with NSCLC underwent (99m)Tc-MIBI single-photon emission tomography (SPET) before chemotherapy. In 19 patients both Pgp and p53 expression, and in two patients only p53 expression (due to the limited biopsy material), were measured with immunohistochemical staining. (99m)Tc-MIBI uptake was significantly higher in responders than in non-responders: 3.09+/-1.14 vs 2.24+/-0.88 ( P<0.03) and 3.09+/-1.08 vs 2.37+/-1.06 ( P<0.05) for the early ratio (ER) and the delayed ratio (DR), respectively. The wash-out rate (WR) of responders was not significantly different from that of non-responders. We found no significant differences in ER, DR and WR among the groups positive or negative for Pgp and p53 status. There was a significant positive correlation between the survival rate and both ER and DR: r=0.49 ( P=0.003) and r=0.40 ( P=0.018), respectively. Patients with ER and DR values above 3 showed significantly longer survival than those with values below 3: 14.7+/-8.5 months vs 7.3+/-5.1 months ( P<0.009) and 13.2+/-8.4 months vs 7.4+/-5.3 months ( P<0.04) for ER and DR, respectively. However, interestingly, and in contrast to expectations, patients with a Pgp score of +2 showed significantly longer survival (12.9+/-6.7 months) than those with Pgp scores of +1 (4.4+/-3.0 months) or - (negative) (3.8+/-2.2 months) ( P<0.009 and P<0.02, respectively). Our results suggest that in NSCLC, patients with higher (99m)Tc-MIBI uptake tend to show a positive response to chemotherapy, and patients with ER and DR values above 3 have a significantly better prognosis. We also found that Pgp expression seems to play only a minor role in (99m)Tc-MIBI uptake. Our finding that patients with ER and DR values above 3 have a better prognosis needs to be confirmed in larger series of patients.

Cost-Effectiveness of 99mTc-Sestamibi in Predicting Response to Chemotherapy in Patients with Lung Cancer: Systematic Review and Meta-Analysis

“…It has been shown that 99m Tc-MIBI is a transport substance recognized by multidrug resistance (MDR)-related P glycoprotein (P-gp) and that tumor cell accumulation is enhanced by inhibition of the efflux transport function (7). These results provided the basis for clinical studies that investigated the role of 99m Tc-MIBI in predicting the response to chemotherapy in patients with lung cancer (8)(9)(10)(11)(12)(13)(14)(15).…”

F-18-2-Fluoro-2-Deoxyglucose Positron Emission Tomography Compared to Technetium-99m Hexakis-2-Methoxyisobutyl Isonitrile Single Photon Emission Chest Tomography in the Diagnosis of Indeterminate Lung Lesions

“…In addition, 18 FDG uptake is related to the proliferation potential of lung cancer, which is lower in BAC than in non-BAC [15]. In contrast, MIBI accumulation depends on several factors as lesional blood flow, mitochondrial membrane potentials and P-glycoprotein expression [16,17]. Although the precise mechanism is not clear, we hypothesize that blood flow might mainly contribute to the increased MIBI uptake in BAC.…”

Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma

“…Furthermore, 99m Tc-MIBI single-photon emission tomography can correctly predict chemotherapy response in lung cancer patients. Lower tumour-to-normal lung ratios were found in patients with no remission or progression as compared to those in patients with partial or complete response to subsequent treatment [3,27,28]. Interestingly, in these patients 99m Tc-MIBI wash-out from lung tumours did not correlate with tumour response, indicating that the Pgp-dependent outward transport of drugs is not the major cause of intrinsic resistance in these tumours.…”