Correlation of 4'-[methyl-(11)C]-thiothymidine uptake with Ki-67 immunohistochemistry and tumor grade in patients with newly diagnosed gliomas in comparison with (11)C-methionine uptake.
OBJECTIVE
A novel radiopharmaceutical, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. The purpose of this study was to evaluate (11)C-4DST uptake in patients with newly diagnosed glioma and to correlate the results with proliferative activity and tumor grade, in comparison with L-[methyl-(11)C]-methionine ((11)C-MET).


METHODS
Investigations of (11)C-4DST and (11)C-MET PET/CT were performed retrospectively in 23 patients with newly diagnosed glioma. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) was defined as the volume with a threshold of 40% of the SUVmax. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.


RESULTS
Of 23 gliomas examined, (11)C-4DST PET/CT and (11)C-MET PET/CT detected 20 and 22, respectively. Linear regression analysis between (11)C-4DST and (11)C-MET indicated a weak correlation for SUVmax (r = 0.54, P < 0.008), for T/N ratio (r = 0.56, P < 0.006), and for MTV (r = 0.60, P < 0.003). Linear regression analysis indicated a weak correlation between (11)C-4DST and Ki-67 index for SUVmax (r = 0.46, P < 0.03), for T/N ratio (r = 0.43, P < 0.05), and for MTV (r = 0.68, P < 0.001) and between (11)C-MET MTV and Ki-67 index (r = 0.43, P < 0.04). Using (11)C-4DST, there was a significant difference in SUVmax between grades II and IV (P < 0.03) and in MTV between grades II and IV (P < 0.009) and grades III and IV (P < 0.02). Using (11)C-MET, there was a significant difference in SUVmax (P < 0.009) and T/N ratio (P < 0.02) between grades II and IV and in MTV between grades II and IV (P < 0.03) and grades III and IV (P < 0.02).


CONCLUSIONS
(11)C-4DST PET/CT is feasible for imaging of brain gliomas, as well as (11)C-MET PET/CT. Especially, it showed the highest correlation coefficient between (11)C-4DST MTV and Ki-67 index in newly diagnosed gliomas.
Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Kenichi
K
Tanaka
Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. yuka@kms.ac.jp.
Yuka
Y
Yamamoto
Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Yukito
Y
Maeda
Department of Medical Physics, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
Hiroyuki
H
Yamamoto
Department of Medical Physics, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
Nobuyuki
N
Kudomi
Department of Neurosurgery, Kagawa General Rehabilitation Hospital, Takamatsu, Kagawa, Japan.
Nobuyuki
N
Kawai
Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, Japan.
Jun
J
Toyohara
Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
Yoshihiro
Y
Nishiyama
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D049109:Cell Proliferation; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D013936:Thymidine / Q000031:analogs & derivatives* / Q000378:metabolism; D055815:Young Adult
D002250:Carbon Radioisotopes; D019394:Ki-67 Antigen; C084401:2'-deoxy-4'-methyl-4'-thiothymidine; D008715:Methionine; D013936:Thymidine
11C-4DST; 11C-MET; Glioma; PET; Proliferation