A new tracer, 49-[methyl-11 C]-thiothymidine ( 11 C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. This study evaluated the potential of 11 C-4DST PET/CT for imaging proliferation in nonsmall cell lung cancer (NSCLC), compared with 18 F-FDG PET/ CT. Methods: Eighteen patients with lung lesions were examined by PET/CT using 11 C-4DST and 18 F-FDG. We constructed decay-corrected time-activity curves of 9 major regions as the mean standardized uptake value. We then compared the maximum standardized uptake value (SUVmax) of lung tumors on both 11 C-4DST and 18 F-FDG PET/CT with the Ki-67 index of cellular proliferation and with CD31-positive vessels as a marker of angiogenesis in surgical pathology. Results: NSCLC was pathologically confirmed in 19 lesions of 18 patients. Physiologic accumulation of 11 C-4DST was high in liver, kidney, and bone marrow and low in aorta, brain, lung, and myocardium. Biodistribution of 11 C-4DST was almost stable by 20 min after injection of 11 C-4DST. Mean 11 C-4DST SUVmax for lung cancer was 2.9 6 1.0 (range, 1.5-4.7), significantly different from mean 18 F-FDG SUVmax, which was 6.2 6 4.5 (range, 0.9-17.3; P , 0.001). The correlation coefficient between SUVmax and Ki-67 index was higher with 11 C-4DST (r 5 0.82) than with 18 F-FDG (r 5 0.71). The correlation coefficient between SUVmax and CD31 was low with both 11 C-4DST (r 5 0.21) and 18 F-FDG (r 5 0.21), showing no significant difference between the tracers. Conclusion: A higher correlation with proliferation of lung tumors was seen for 11 C-4DST than for 18 F-FDG. 11 C-4DST PET/CT may allow noninvasive imaging of DNA synthesis in NSCLC.

Background4′-[methyl-11C]-thiothymidine (4DST) is a novel positron emission tomography (PET) tracer to assess proliferation of malignancy. The diagnostic abilities of 4DST and 2-deoxy-2-18 F-fluoro-d-glucose (FDG) for detecting regional lymph node (LN) metastases of non-small cell lung cancer (NSCLC) were prospectively compared. In addition, the relationship between the PET result and the patient's prognosis was evaluated.MethodsA total of 31 patients with NSCLC underwent 4DST PET/computed tomography (CT) and FDG PET/CT. The PET/CT images were evaluated qualitatively and quantitatively for focal uptake of each PET tracer, according to the staging system of the American Joint Committee on Cancer. Surgical and histological results provided the reference standards. Patients were followed for up to two years to assess disease-free survival.ResultsOn a per-lesion basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for LN staging were 82%, 72%, 32%, 96%, and 73%, respectively, for 4DST, and 29%, 86%, 25%, 88%, and 78%, respectively, for FDG. The sensitivity of 4DST was significantly higher than that of FDG (P < 0.001). The disease-free survival rate with positive 4DST uptake in nodal lesions was 0.35, which was considerably lower than the rate of 0.83 with negative findings (P = 0.04). Among the factors tested, nodal staging by 4DST was the most influential prognostic factor (P = 0.05) in predicting the presence of a previously existing spread lesion or of a recurrence over the course of 2 years.Conclusion4DST PET/CT is sensitive for detecting mediastinal lymph node metastasis in NSCLC, but its low specificity is a limitation. However, it may be helpful in predicting the prognosis of NSCLC.

Our retrospective study demonstrates that the indicator for elective general thoracic surgery is not the CD4-positive T-lymphocyte count and that the initiation of HAART may reduce the 12-month mortality rates. In HIV-positive patients, regardless of the CD4-positive T-lymphocyte count, surgeons can operate in the same manner as they would with HIV-negative patients.

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