4'-[Methyl-11C]-thiothymidine PET/CT for proliferation imaging in non-small cell lung cancer

• Published in: Journal of Nuclear Medicine Vol. 53; no. 2; pp. 199 - 206
• Main Authors: Minamimoto, Ryogo, Toyohara, Jun, Seike, Ayako, Ito, Hideyuki, Endo, Hisako, Morooka, Miyako, Nakajima, Kazuhiko, Mitsumoto, Takuya, Ito, Kimiteru, Okasaki, Momoko, Ishiwata, Kiichi, Kubota, Kazuo
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.02.2012
• Subjects: Aged; Aged, 80 and over; Biological Transport; Brain; Brain cancer; Cancer therapies; Carbon Radioisotopes; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell cycle; Cell Proliferation; Deoxyribonucleic acid; DNA; Drug dosages; Female; Humans; Incorporation; Ki-67 Antigen - metabolism; Lung - diagnostic imaging; Lung - metabolism; Lung - pathology; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Middle Aged; Multimodal Imaging; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Positron-Emission Tomography; Thymidine - analogs & derivatives; Thymidine - metabolism; Tomography, X-Ray Computed; Tumors; Whole Body Imaging
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.111.095539

A new tracer, 4'-[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 non-small cell lung cancer (NSCLC), compared with (18)F-FDG PET/CT. 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. 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 ± 1.0 (range, 1.5-4.7), significantly different from mean (18)F-FDG SUVmax, which was 6.2 ± 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 = 0.82) than with (18)F-FDG (r = 0.71). The correlation coefficient between SUVmax and CD31 was low with both (11)C-4DST (r = 0.21) and (18)F-FDG (r = 0.21), showing no significant difference between the tracers. 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.