4′-[Methyl-¹¹C]-Thiothymidine PET/CT for Proliferation Imaging in Non–Small Cell Lung Cancer

Abstract

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.

A pilot study of 4′-[methyl-11C]-thiothymidine PET/CT for detection of regional lymph node metastasis in non-small cell lung cancer

“…In our previous report, we demonstrated the great potential of 4DST-PET/CT for proliferation imaging in lung cancer itself [27]. Moreover, we showed a case which indicated the potential of 4DST for the detection of LN metastasis in NSCLC [27]. The background 4DST uptake in mediastinum was lower than that of FDG; therefore, we hypothesize that 4DST might have an advantage for detecting mediastinal lymph node metastasis.…”

“…A part of data from 18 of these patients was used in the previous study [27]. All patients underwent CECT before 4DST-PET/CT and FDG-PET/CT.…”

“…Recently, a thymidine analog, carbon-11-labeled 4′-thiothymidine ([ 11 C] 4DST, originally designated as [ 11 C]S-dThd), was introduced as a cell proliferation imaging agent based on its mechanism of incorporation into DNA [24-26]. In our previous report, we demonstrated the great potential of 4DST-PET/CT for proliferation imaging in lung cancer itself [27]. Moreover, we showed a case which indicated the potential of 4DST for the detection of LN metastasis in NSCLC [27].…”

Correlation of 4′-[methyl-11C]-Thiothymidine Uptake with Ki-67 Immunohistochemistry in Patients with Newly Diagnosed and Recurrent Gliomas

“…Minamimoto et al evaluated 4DST uptake and Ki-67 index in patients with non-small cell lung cancer [13]. They showed a significant correlation between 4DST maximal SUV and Ki-67 index [13]. However, Ito et al showed no significant correlation between 4DST maximal SUV and Ki-67 index in head and neck squamous cell carcinoma [14].…”

“…The present study also showed a weak correlation between 4DST T/N ratio and Ki-67 index in newly diagnosed gliomas. Minamimoto et al evaluated 4DST uptake and Ki-67 index in patients with non-small cell lung cancer [13]. They showed a significant correlation between 4DST maximal SUV and Ki-67 index [13].…”