Effects of radiotherapy on the cellular uptake of carbon-14 labeledl-methionine in tumor tissue

Kubota, Keiichi; Kubota, Roko; Yamada, S.; Tada, Masao

doi:10.1016/0969-8051(94)00099-6

Cited by 15 publications

(9 citation statements)

References 11 publications

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“…14 C-Methionine uptake in the granuloma at 15 and 30 min was also significantly lower than that in the tumor-61% and 45%, respectively, of tumor uptake. These results were consistent with the present results, although 14 Cmethionine uptake in the tumor and granuloma at 60 min was lower than that at 15 and 30 min. The biodistribution at early time points supports our results in the present study.…”

Section: Discussionsupporting

confidence: 83%

“…L-[methyl- 14 C]methionine (specific activity, 1.48-2.04 GBq/mmol) and [methyl-3 H (N)]-39-fluoro 39-deoxythymidine ( 3 H-FLT) (specific activity, 74-370 GBq/mmol) were purchased from American Radiolabeled Chemicals, Inc., and Moravek Biochemicals Inc.…”

Section: Radiopharmaceuticalsmentioning

confidence: 99%

“…On the other hand, 11 C-methionine uptake reflects increased amino acid transport and protein synthesis and is related to cellular proliferation. 11 C-Methionine has been shown to possess a high specificity in tumor detection, tumor delineation, and differentiation of benign from malignant lesions (12,13) because of the lower uptake of 11 C-methionine than of 18 F-FDG in inflammatory cells (14)(15)(16). These factors suggest that thymidine or amino acid tracers are potentially more suitable than 18 F-FDG for the differentiation of tumors from inflammatory lesions.…”

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confidence: 99%

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Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT

Zhao

Kuge²,

Kohanawa³

et al. 2007

J Nucl Med

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Many clinical PET studies have shown that increased 18F-FDG uptake is not specific to malignant tumors. 18F-FDG is also taken up in inflammatory lesions, particularly in granulomatous lesions such as sarcoidosis or active inflammatory processes after chemoradiotherapy, making it difficult to differentiate malignant tumors from benign lesions, and is the main source of falsepositive 18F-FDG PET findings in oncology. These problems may be overcome by multitracer studies using 39-deoxy- 39-18F-fluorothymidine (18F-FLT) or L-11C-methionine. However, 18F-FLT or 11C-methionine uptake in granulomatous lesions remains unclarified. In this study, the potentials of 18F-FLT and 11C-methionine in differentiating malignant tumors from granulomaswere comparedwith 18F-FDGusing experimental ratmodels. Methods: Dual-tracer tissue distribution studies using 18F-FDG and 3H-FLT (groups I and III) or 18F-FDG and 14C-methionine (groups II and IV)were performed on rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Gue´ rin [BCG]–induced) and hepatomas (KDH-8–induced) (groups I and II) or on rats bearing both turpentine oil–induced inflammation and hepatomas (groups III and IV). One hour after the injection of a mixture of 18F-FDG and 3H-FLT or of 18F-FDG and 14C-methionine, tissues were excised to determine the radioactivities of 18F-FDG, 3H-FLT, and 14C-methionine (differential uptake ratio). Results: Mature epithelioid cell granuloma formation and massive lymphocyte infiltration were observed in the granuloma tissue induced by BCG, histologically similar to sarcoidosis. The granulomas showed high 18F-FDG uptake comparable to that in the hepatomas (group I, 8.18 6 2.40 vs. 9.13 6 1.52, P 5 NS; group II, 8.43 6 1.45 vs. 8.91 6 2.32, P 5 NS). 14C-Methionine uptake in the granuloma was significantly lower than that in the hepatoma (1.31 6 0.22 vs. 2.47 6 0.60, P , 0.01), whereas 3H-FLT uptake in the granuloma was comparable to that in the hepatoma (1.98 6 0.70 vs. 2.30 6 0.67, P 5 NS). Mean uptake of 18F-FDG, 3H-FLT, and 14C-methionine was markedly lower in the turpentine oil–induced inflammation than in the tumor. Conclusion: 14C-Methionine uptake was significantly lower in the granuloma than in the tumor, whereas 18F-FDG and 3H-FLT were not able to differentiate granulomas from tumors. These results suggest that 14C-methionine has the potential to accurately differentiate malignant tumors frombenign lesions, particularly granulomatous lesions, providing a biologic basis for clinical PET studies

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Section: Discussionsupporting

confidence: 83%

Section: Radiopharmaceuticalsmentioning

confidence: 99%

mentioning

confidence: 99%

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Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT

Zhao

Kuge²,

Kohanawa³

et al. 2007

J Nucl Med

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“…Positron emission tomography with the glucose analogue fluorine-18 fluorodeoxyglucose (FDG-PET) has significantly improved the accuracy of LN staging [2]. However, FDG shows substantial uptake in human [3,4] and experimental inflammatory lesions [5,6,7,8,9,10,11,12], and uptake of FDG in acute inflammatory reactions is a well-recognized limitation of FDG-PET that gives rise to false positive results in a considerable percentage of cases.…”

Section: Introductionmentioning

confidence: 99%

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

et al. 2002

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High uptake of [(18)F]fluoro-2-deoxy- D-glucose (FDG) by inflammatory cells is a frequent cause of false positive results in lymph node (LN) staging by positron emission tomography. Previous studies suggest that radiolabelled amino acids may be more specific markers for viable tumour tissue than FDG. The aim of this study was to investigate quantitatively the uptake of FDG, [(3)H]methyl- L-methionine (MET) and O-2-([(18)F]fluoroethyl)- L-tyrosine (FET) in tumour-infiltrated and immunologically stimulated LNs. Popliteal LNs of Balb/c and DBA/2 mice were stimulated by injection into the right posterior foot pad of mice of either streptozotocin (STZ), causing chronic lymphadenitis, or concanavalin A (Con A), resulting in acute lymphadenitis. Tumour-infiltrated popliteal LNs were induced by inoculation of 2x10(5) lacZ-tagged T cell mouse lymphoma cells into the right posterior foot pad of syngeneic mice. Twenty-one days post inoculation of tumour cells or at various time points after STZ or Con A injection, mice were simultaneously injected intravenously with MET and FDG or MET and FET. After 30 min, mice were sacrificed and tracer uptake was determined in popliteal LNs. Contralateral LNs and LNs of untreated mice served as controls. Histopathological and immunohistochemical analysis demonstrated typical signs of chronic inflammation (non-specific sinus hyperplasia with macrophages) in STZ-treated animals and acute inflammatory changes (accumulation of neutrophilic granulocytes, vascular dilation, follicular hyperplasia) in Con A-treated animals. X-Gal staining confirmed the presence of tumour cells in the LNs of the injected side of tumour-inoculated mice. In the chronic lymphadenitis model, FDG uptake increased 3.0+/-0.1 fold [from 2.7+/-0.2 to 8.2+/-1.2 percent of injected dose per gram tissue (%ID/g)] and MET uptake 2.0+/-0.01 fold (from 4.5+/-0.6 to 9.2+/-1.1 %ID/g). In the acute lymphadenitis model, FDG uptake increased 3.9+/-0.3 fold (from 2.7+/-0.2 to 10.6+/-2.4 %ID/g) and MET uptake 1.9+/-0.1 fold (from 4.5+/-0.6 to 8.5+/-1.4 %ID/g). In contrast, FET uptake in both lymphadenitis models (1.0+/-0.03 and 1.2+/-0.04 fold) was not significantly different from that in controls (from 4.2+/-0.3 to 4.7+/-0.7 and to 5.1+/-0.4 %ID/g, respectively). Uptake of all three tracers in tumour-infiltrated LNs was significantly higher than that in control LNs. FDG uptake increased 2.8+/-0.15 fold (from 2.7+/-0.2 to 7.6+/-1.3%ID/g), MET uptake 1.7+/-0.11 fold (from 4.5+/-0.6 to 7.5+/-1.3 %ID/g) and FET uptake 2.4+/-0.15 fold (from 4.2+/-0.3 to 10.0+/-1.8 %ID/g). MET and FDG uptake was similar or higher in inflammatory than in tumour-infiltrated LNs ( P=0.01 and P<0.01, respectively). In contrast, uptake of FET showed no overlap between tumour-infiltrated and inflammatory LNs ( P<0.00001). In conclusion, tumour-infiltrated and inflammatory LNs could not be differentiated by means of FDG and MET uptake. FET, in contrast, proved to be a specific tracer for differentiating between tumour-infiltrated and inflammatory LNs in the murin...

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“…11 C-MET uptake reflects increased amino acid transport and protein synthesis and is related to cellular proliferation activity. 11 C-MET has been shown to possess a high specificity in tumor detection, tumor delineation, and differentiation of benign from malignant lesions [8], owing to the lower uptake level of 11 C-MET in inflammatory cells than that of 18 F-FDG [9][10][11]. Several authors have reported on trials of 11 C-MET for the evaluation of brain tumors and other malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

Kuge

Zhao

et al. 2011

Eur J Nucl Med Mol Imaging

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Purpose: We evaluated whether the dynamic profile of 11 C-MET may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small-animal PET.Methods: Rhodococcus aurantiacus and allogenic rat C6-glioma cells were inoculated respectively into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n=6). Ten days after the inoculations, dynamic 11 C-MET PET was performed by small-animal PET up to 120 min after injection of 11 C-MET. The next day, after overnight fasting, the rats were injected with 18 F-FDG, and dynamic 18 F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. Results:11 C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11 C-MET uptake in the granuloma was significantly different from that in the tumor (p<0.001). In the static analysis of 11 C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 ± 0.09) was significantly lower than that in the tumor (1.72 ± 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of 18 F-FDG in the granuloma were similar to those in the tumor (p=ns). Conclusions: Dynamic 11C-MET PET has an additional value for differentiating malignant tumors from 3 granulomatous lesions, which deserve further elucidation in clinical settings.

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Effects of radiotherapy on the cellular uptake of carbon-14 labeledl-methionine in tumor tissue

Cited by 15 publications

References 11 publications

Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT

Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

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Effects of radiotherapy on the cellular uptake of carbon-14 labeledl-methionine in tumor tissue

Cited by 15 publications

References 11 publications

Usefulness of 11C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with 18F-FDG and 18F-FLT

Usefulness of 11C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with 18F-FDG and 18F-FLT

O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

Contact Info

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Resources

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Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT

Usefulness of ¹¹C-Methionine for Differentiating Tumors from Granulomas in Experimental Rat Models: A Comparison with ¹⁸F-FDG and ¹⁸F-FLT