Clinical value of PET/CT with carbon-11 4DST in the evaluation of malignant and benign lung tumors

Objectives: The aim of this study was to assess the clinical value of [¹¹C]4DST uptake in patients with lung nodules, including benign and malignant tumors, and to assess the correlation between [¹¹C]4DST uptake and proliferative activity of tumors in comparison with [¹⁸F]FDG uptake. Methods: Twenty-six patients (22 males and 4 females, mean age of 65.5-year-old) were analyzed in this prospective study. Patients underwent [¹¹C]4DST and [¹⁸F]FDG PET/CT imaging on the same day. Diagnosis of each lung nodule was confirmed by histopathological examination of tissue specimens at surgery, or during clinical follow-up after the PET/CT studies. To assess the utility of the semi-quantitative evaluation method, the SUV_max was calculated of [¹¹C]4DST and [¹⁸F]FDG uptake by the lesion. Proliferative activities of each tumor as indicated by the immunohistochemical Ki-67 index was also estimated using surgical specimens of patients. Then the relationship between the SUV_max of both PET/CT and the Ki-67 index was examined. Furthermore, the relationship between the uptake of [¹¹C]4DST or [¹⁸F]FDG and the histopathological findings, the clinical stage, and the clinical outcome of patients were also assessed. Results: There was a positive linear relationship between the SUV_max of [¹¹C]4DST images and the Ki-67 index (Correlation coefficients = 0.68). The SUV_max of [¹¹C]4DST in the 26 lung nodules were 1.65 ± 0.40 for benign lesions, 3.09 ± 0.83 for adenocarcinomas (P < 0.001 between benign and adenocarcinoma), and 2.92 ± 0.58 for SqCCs (P < 0.001 between benign and SqCC). Whereas, the SUVmax of [¹⁸F]FDG were 2.38 ± 2.27 for benign lesions, 6.63 ± 4.24 for adenocarcinomas (n.s.), and 7.52 ± 2.84 for SqCCs (n.s.). The relationship between TNM tumor stage and the SUV_max of [¹¹C]4DST were 2.54 ± 0.37 for T1, 3.48 ± 0.57 for T2, and 4.17 ± 0.72 for T3 (P < 0.005 between T1 and T2, and P < 0.001 between T1 and T3). In comparison with the TNM pathological stage, SUVmax of [¹¹C]4DST were 2.63 ± 0.49 for stage I, 3.36 ± 0.23 for stage II, 3.40 ± 1.12 for stage III, and 4.65 for stage IV (P < 0.05 between stages I and II). In comparison of the clinical outcome, the SUV_max of [¹¹C]4DST were 2.72 ± 0.56 for the no recurrence (No Rec.) group, 3.10 ± 0.33 for the recurrence-free with adjuvant chemotherapy after the surgery (the No Rec. Adjv. CTx. group) and 4.66 ± 0.02 for the recurrence group (Rec. group) (P < 0.001 between the No Rec and Rec. groups, and P < 0.005 between the No Rec. Adjv. CTx. and Rec. groups). Conclusions: PET/CT with [¹¹C]4DST is as feasible for imaging of lung tumors as [¹⁸F]FDG PET/CT. For diagnosing lung tumors, [¹¹C]4DST PET is useful in distinguishing benign nodules from malignancies. [¹¹C]4DST uptake in lung carcinomas is correlated with the proliferative activity of tumors, indicating a promising noninvasive PET imaging of DNA synthesis in malignant lung tumors.