Comparative study of ¹⁸F-FDG-PET/CT imaging and serum hTERT mRNA quantification in cancer diagnosis

Abstract

We have reported on the clinical usefulness of human telomerase reverse transcriptase (hTERT) mRNA quantification in sera in patients with several cancers. Positron emission tomography-computed tomography (PET/CT) using ¹⁸F-fluorodeoxyglucose (FDG) has recently become an excellent modality for detecting cancer. We performed a diagnostic comparative study of FDG-PET/CT and hTERT mRNA quantification in patients with cancer. Four hundred seventy subjects, including 125 healthy individuals and 345 outpatients with cancer who had received medical treatments for cancer in their own or other hospitals, were enrolled. The subjects were diagnosed by FDG-PET/CT, and we measured their serum hTERT mRNA levels using real-time RT-PCR, correlating the quantified values with the clinical course. In this prospective study, we statistically assessed the sensitivity and specificity, and their clinical significance. hTERT mRNA and FDG-PET/CT were demonstrated to be correlated with the clinical parameters of metastasis and recurrence (P < 0.001), and of recurrence and tumor number in cancer compared with noncancer patients, respectively. A multivariate analysis showed a significant difference in the detection by FDG-PET/CT, ¹⁸F-FDG uptake, the detection by hTERT mRNA, and age. The use of both FDG-PET/CT and hTERT mRNA resulted in a positivity of 94.4% (221/234) for the detection of viable tumor cells. FDG-PET/CT is superior to hTERT mRNA quantification in the early detection of cancer and combinative use of FDG-PET/CT and hTERT mRNA may improve the diagnostic accuracy of cancer.

Keywords: 18F-FDG; PET/CTPET/CT; cancer; diagnosis; hTERTmRNA.

Figure 1

The classification of the subjects enrolled in this study. The study population of 470 individuals was divided into two groups consisting of 241 consecutive patients and 229 nonconsecutive individuals, including 125 healthy individuals for medical examination (see the Materials and Methods section for details).

Figure 2

(A) The ROC curve analyses are shown separately according to the results before (left: N = 229) and after (middle) therapy. Although the analysis of hTERT mRNA in the total study population resulted in a sensitivity of 66.7% and a specificity of 69.5%, when the data were limited to only the data obtained before therapy, the specificity of hTERT mRNA increased to 79.6%. However, FDG-PET/CT had a sensitivity of more than 90.0% and a specificity of more than 81.0% (Fig. S2). The cut-off value was 907 copies/200 μL. (B) The hTERT mRNA levels were statistically analyzed according to the following variables: therapy status (before or after), tumor number, presence or absence of metastasis, presence or absence of recurrence, and FDG uptake [SUV max (late − early)]. There were significant differences in metastasis and recurrence according to a t-test (**P < 0.01 for each). ROC, receiver operating characteristic; hTERT, human telomerase reverse transcriptase; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography; SUV, standardized uptake value.

Figure 3

A representative case of a patient with lung cancer. The diagnosis was confirmed by needle aspiration cytology. The top and bottom columns include four images (PET-CT, axial view of PET [MIP: image], axial view of CT, and fusion image [selected transaxial fused PET/CT slice] from the right to left); the bottom images were acquired a year after the top images to enable a more precise diagnosis. The fusion image was used for enhancing FDG accumulation on selected slice. The first PET-CT study did not diagnose the findings (shown by an arrowhead) as indicative of malignancy yet. The hTERT mRNA increased from 964 to 3245 copies in the 1-year interval between imaging studies, with both values indicating positivity. The bottom images demonstrate the increased size of a lung tumor over time, suggesting the potential use of hTERT mRNA quantification as a complementary diagnostic technique. PET, positron emission tomography; CT, computed tomography; MIP, maximum intensity projection; FDG, fluorodeoxyglucose; hTERT, human telomerase reverse transcriptase.