Feasibility studies of 4′-[methyl-11C]thiothymidine as a tumor proliferation imaging agent in mice

Toyohara, Jun; Okada, Maki; Toramatsu, Chie; Suzuki, Kazutoshi; Irie, Toshiaki

doi:10.1016/j.nucmedbio.2007.10.001

Cited by 53 publications

(45 citation statements)

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“…Moreover, 14 C-4DST has shown significantly higher uptake into proliferating tissues than FLT labeled with 3 H at the methyl group, a result supported by an animal study using 11 C-4DST (10). In a human study using 11 C-4DST, Toyohara et al showed that true input curves after metabolite analysis and dynamic brain tumor imaging resulted in a linear Patlak plot over 10-90 min after injection and suggested metabolic incorporation of 4DST into higher molecules, such as DNA (11).…”

mentioning

confidence: 75%

“…Currently, we have no detailed information on the affinities or subtype selectivities of 4DST toward nucleoside transporters and thymidine kinase. Despite a high serum thymidine concentration, previous rodent studies of 11 C-4DST have been performed with no phosphorylase pretreatment (9,10). Therefore, in contrast to 18 F-FLT, competition of endogenous thymidine for 11 C-4DST uptake appears negligible.…”

Section: Discussionmentioning

confidence: 99%

“…The structure of 11 C-4DST has the 49-oxo of thymidine replaced by 49-sulfur, so as to closely resemble the structure of thymidine (16). An in vitro study proved that 3 H-4DST is incorporated into DNA (17), and 14 C-4DST was confirmed to show metabolism similar to that of thymidine, maintaining stability in the blood (9,10). In a human study, Toyohara et al used Patlak graphical analysis to obtain the 11 C-4DST flux constant (K i ), and K i values of 11 C-4DST correlated well with standardized uptake value (11).…”

Section: Discussionmentioning

confidence: 99%

“…Toyohara et al developed 49-thiothymidine labeled with 11 C at the methyl group (49-[methyl-11 C]-thiothymidine [ 11 C-4DST], previously designated as 11 C-S-dThd) as a new candidate tracer for cell proliferation imaging that is resistant to degradation by thymidine phosphorylase and is incorporated into DNA (9,10). Moreover, 14 C-4DST has shown significantly higher uptake into proliferating tissues than FLT labeled with 3 H at the methyl group, a result supported by an animal study using 11 C-4DST (10).…”

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confidence: 99%

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

Minamimoto¹,

Toyohara²,

Seike³

et al. 2011

J Nucl Med

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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.

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confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Minamimoto¹,

Toyohara²,

Seike³

et al. 2011

J Nucl Med

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“…Toyohara et al developed 4 0 -thiothymidine labeled with 11 C at the methyl group (4 0 -[methyl-11 C]-thiothymidine [4DST]), as a new candidate for cell proliferation imaging that is resistant to degradation by thymidine phosphorylase and is incorporated into DNA [7,8]. A 11 C-4DST PET pilot study of 6 patients with various brain tumors showed that 11 C-4DST PET is feasible for brain tumor imaging and can be performed with acceptable dosimetry and pharmacologic safety at a suitable dose for adequate imaging [9].…”

Section: Introductionmentioning

confidence: 99%

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

Yamamoto

Nishiyama

2016

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

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Purpose: 4 0 -[methyl-11 C]-thiothymidine (4DST) has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. We evaluated 4DST uptake on PET in patients with newly diagnosed and recurrent gliomas and correlated the results with proliferative activity.Methods: 4DST PET was investigated in 32 patients, including 21 with newly diagnosed gliomas and 11 with recurrent gliomas. PET imaging was performed at 15 min after 4DST injection. The standardized uptake value (SUV) was determined by region-of-interest analysis. The maximal SUV for tumor (T) and the mean SUV for contralateral normal brain tissue (N) were calculated and T/N ratio was determined. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.Results: The sensitivity of 4DST PET for the detection of newly diagnosed and recurrent gliomas was 86 % and 100 %, respectively. In newly diagnosed gliomas, there was a weak correlation between T/N ratio and Ki-67 index (r ¼ 0.45; p < 0.05). In recurrent gliomas, there was no significant difference between T/N ratio and Ki-67 index.Conclusion: In newly diagnosed gliomas, 4DST PET seems to be useful in the noninvasive assessment of proliferation.

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Pd‐mediated rapid cross‐couplings using [¹¹C]methyl iodide: groundbreaking labeling methods in ¹¹C radiochemistry

Doi¹

2015

Labelled Comp Radiopharmac

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Prof. Bengt Långström is a pioneer in the field of chemistry-driven positron emission tomography (PET) imaging. He has developed a variety of excellent radiolabeling methodologies using the methods of organic chemistry, with the aim of widening the potential of PET in the study of life. Among his groundbreaking achievements in (11) C radiochemistry, there is the discovery of the Pd-mediated rapid cross-coupling reaction using [(11) C]methyl iodide. It was first reported by his Uppsala group in 1994-1995 and was further investigated by his and other groups with a view of enhancing its generality and practicability. This reaction is currently considered one of the basic methods for (11) C-labeling of low-weight organic compounds. This paper presents a short summary of the background and the development of Pd-mediated rapid cross-couplings of [(11) C]methyl iodide, with a focus not only on organostannanes, but also on organoboranes, organozincs, and terminal acetylene compounds. All these reactions have proven to be dependable (11) C-labeling methodologies that use chemically reliable carbon-carbon bond formation reactions.

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Feasibility studies of 4′-[methyl-11C]thiothymidine as a tumor proliferation imaging agent in mice

Cited by 53 publications

References 20 publications

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

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

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

Pd‐mediated rapid cross‐couplings using [¹¹C]methyl iodide: groundbreaking labeling methods in ¹¹C radiochemistry

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Feasibility studies of 4′-[methyl-11C]thiothymidine as a tumor proliferation imaging agent in mice

Cited by 53 publications

References 20 publications

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

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

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

Pd‐mediated rapid cross‐couplings using [11C]methyl iodide: groundbreaking labeling methods in 11C radiochemistry

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

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

Pd‐mediated rapid cross‐couplings using [¹¹C]methyl iodide: groundbreaking labeling methods in ¹¹C radiochemistry