Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

Miyakubo, Mitsuyuki; Oriuchi, Noboru; Tsushima, Yoshito; Higuchi, Tetsuya; Koyama, Keiko; Arai, Kiyokazu; Paudyal, Bishnuhari; Iida, Yasuhiko; Hanaoka, Hirofumi; Ishikita, Tomohiro; Nakasone, Yutaka; Negishi, Akihide; Mogi, Kenji; Endo, Keigo

doi:10.1007/bf03033991

Cited by 31 publications

(19 citation statements)

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“…2-76 Br-BAMP provided the visualization of tumorous lesions more clearly than did 18 F-FAMT, indicating the high potential of 2-76 Br-BAMP as a new tumor imaging PET probe. Although human studies are needed, 2-76 Br-BAMP may detect various tumors such as lung and brain tumors, lymphomas, melanomas, and maxillofacial tumors as well as 18 F-FAMT does (24)(25)(26)(27). In addition to the relatively long halflife of 76 Br, 2-76 Br-BAMP exhibited slower elimination rates from the tumor than from the kidney, and thus a delayed-phase scan may visualize the tumor even if it is in the urinary tract.…”

Section: Discussionmentioning

confidence: 99%

Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

et al. 2015

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Radiolabeled amino acids are superior PET tracers for the imaging of malignant tumors, and amino acids labeled with 76 Br, an attractive positron emitter because of its relatively long half-life (16.2 h), could potentially be a widely usable tumor imaging tracer. In this study, in consideration of its stability and tumor specificity, we designed two 76 Br-labeled amino acid derivatives, 2-76 Br-bromo-α-methyl-L-phenylalanine (2-76 Br-BAMP) and 4-76 Br-bromo-α-methyl-L-phenylalanine (4-76 Br-BAMP), and investigated their potential as tumor imaging agents. Methods: Both 76 Br-and 77 Br-labeled amino acid derivatives were prepared. We performed in vitro and in vivo stability studies and cellular uptake studies using the LS180 colon adenocarcinoma cell line. Biodistribution studies in normal mice and in LS180 tumor-bearing mice were performed, and the tumors were imaged with a small-animal PET scanner. Results: Both 77 BrBAMPs were stable in the plasma and in the murine body. Although both 77 Br-BAMPs were taken up by LS180 cells and the uptake was inhibited by L-type amino acid transporter 1 inhibitors, 2-77 Br-BAMP exhibited higher uptake than 4-77 Br-BAMP. In the biodistribution studies, 2-77 Br-BAMP showed more rapid blood clearance and lower renal accumulation than 4-77 Br-BAMP. More than 90% of the injected radioactivity was excreted in the urine by 6 h after the injection of 2-77 Br-BAMP. High tumor accumulation of 2-77 Br-BAMP was observed in tumor-bearing mice, and PET imaging with 2-76 Br-BAMP enabled clear visualization of the tumors. Conclusion: 2-77 Br-BAMP exhibited preferred pharmacokinetics and high LS180 tumor accumulation, and 2-76 Br-BAMP enabled clear visualization of the tumors by PET imaging. These findings suggest that 2-76 Br-BAMP could constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers. Iti s well recognized that 18 F-FDG PET has had a great impact in tumor imaging and monitoring the response of tumors to chemotherapy. However, the high accumulations of 18 F-FDG that can occur in nontarget tissues such as the brain and inflammatory sites invoke the need for other PET tracers that could complement or replace 18 F-FDG (1,2). Among them, amino acid tracers such as 11 C-methionine, O-18 F-fluoromethyl-L-tyrosine, O-18 F-fluoroethyl-L-tyrosine, and 3-18 F-fluoro-a-methyl-L-tyrosine ( 18 F-FAMT) have already been introduced into clinical practice (1,3,4). However, their widespread application in clinical studies is limited by the short halflives of 11 C and 18 F. It may be possible to deliver an 18 F-labeled amino acid tracer as is done with 18 F-FDG, but the development of PET tracers using radionuclides with longer half-lives may constitute a way to circumvent the problem.Among the positron emission radionuclides, 76 Br has been proposed as an attractive candidate for using PET (decay mode: b 1 5 57%, electron capture 5 43%). 76 Br can be produced with a low-energy cyclotron by the nuclear reaction of 76 Se(p,n) 76 Br (5). The ...

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Section: Discussionmentioning

confidence: 99%

Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

et al. 2015

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“…The potential of L-type amino acid transporter 1 as a therapeutic target in oral cancer has been described long before (34,35). We designed 18 F-FAMT as a specific PET radiotracer for L-type amino acid transporter 1 that is overexpressed exclusively in malignant tumors (12) and performed several clinical trials in comparison with 18 F-FDG in oral malignancies (10,14,19). Therefore, analysis of 18 F-FAMT and its corresponding tumor pathologic characteristics is fundamental for the development of a PET imaging-based comprehensive diagnosis of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

“…With a predetermined pathologically confirmed cutoff SUV of 3.0 for 18 F-FDG and 1.4 for 18 F-FAMT from previous PET study of maxillofacial tumors (19), PET volume computerized-assisted reporting performs autosegmentation to the threshold-defined volumes and automatically calculates MTV and average SUV (10). TLG of 18 F-FDG was calculated by multiplying MTV with the average SUV within that volume.…”

Section: Radiopharmaceuticals and Pet Image Analysismentioning

confidence: 99%

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Effects of Intratumoral Inflammatory Process on ¹⁸F-FDG Uptake: Pathologic and Comparative Study with ¹⁸F-Fluoro-α-Methyltyrosine PET/CT in Oral Squamous Cell Carcinoma

et al. 2014

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The accurate depiction of both biologic and anatomic profiles of tumors has long been a challenge in PET imaging. An inflammation, which is innate in the carcinogenesis of oral squamous cell carcinoma (OSCC), frequently complicates the image analysis because of the limitations of 18 F-FDG and maximum standardized uptake values (SUV max ). New PET parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as well as 18 Ffluoro-α-methyltyrosine ( 18 F-FAMT), a malignancy-specific amino acid-based PET radiotracer, are considered more comprehensive in tumor image analysis. Here, we showed the substantial effects of the intratumoral inflammatory process on 18 F-FDG uptake and further study the possibility of MTV and TLG to predict both tumor biology (proliferation activity) and anatomy (pathologic tumor volume). Methods: 18 F-FDG and 18 F-FAMT PET images from 25 OSCC patients were analyzed. SUV max on the tumor site was obtained. PET volume computerized-assisted reporting was used to generate a volume of interest to obtain MTV and TLG for 18 F-FDG and total lesion retention (TLR) for 18 F-FAMT. The whole tumor dissected from surgery was measured and sectioned for pathologic analysis of tumor inflammation grade and Ki-67 labeling index. Results: The high SUV max of 18 F-FDG was related to the high inflammation grade. The SUV max ratio of 18 F-FDG to 18 F-FAMT was higher in inflammatory tumors (P , 0.05) whereas the corresponding value in tumors with a low inflammation grade was kept low. All 18 F-FAMT parameters were correlated with Ki-67 labeling index (P , 0.01). Pathologic tumor volume predicted from MTV of 18 F-FAMT was more accurate (R 5 0.90, bias 5 3.4 ± 6.42 cm 3 , 95% confidence interval 5 0.77-6.09 cm 3 ) than that of 18 F-FDG (R 5 0.77, bias 5 8.1 ± 11.17 cm 3 , 95% confidence interval 5 3.45-12.67 cm 3 ). Conclusion: 18 F-FDG uptake was overestimated by additional uptake related to the intratumoral inflammatory process, whereas 18 F-FAMT simply accumulated in tumors according to tumor activity as evaluated by Ki-67 labeling index in OSCC.

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“…Several clinical studies with small numbers of patients have suggested that FMT is superior to FDG for the detection of musculoskeletal tumors, similar to FDG for the detection of head and neck tumors, and is superior to FDG for determining treatment response in lung cancer. 109,110 Conversely, small clinical studies that used FET indicated that it was generally worse than FDG for the detection of many tumor types, including head and neck cancer. 111,112 FET-PET did exhibit better specificity in several of the studies, raising the possibility that it may be better at differentiating tumor from inflammatory tissue.…”

Section: Imaging Protein and Cell Membrane Metabolismmentioning

confidence: 99%

PET/CT imaging in cancer: Current applications and future directions

Farwell

Pryma

Mankoff

2014

Cancer

196

120

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Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, 18 F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials. Cancer 2014;120:3433-45.

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Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

Cited by 31 publications

References 16 publications

Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Effects of Intratumoral Inflammatory Process on ¹⁸F-FDG Uptake: Pathologic and Comparative Study with ¹⁸F-Fluoro-α-Methyltyrosine PET/CT in Oral Squamous Cell Carcinoma

PET/CT imaging in cancer: Current applications and future directions

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Diagnosis of maxillofacial tumor withl-3-[18F]-fluoro-α-methyltyrosine (FMT) PET: a comparative study with FDG-PET

Cited by 31 publications

References 16 publications

Development of a Widely Usable Amino Acid Tracer: 76Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Development of a Widely Usable Amino Acid Tracer: 76Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Effects of Intratumoral Inflammatory Process on 18F-FDG Uptake: Pathologic and Comparative Study with 18F-Fluoro-α-Methyltyrosine PET/CT in Oral Squamous Cell Carcinoma

PET/CT imaging in cancer: Current applications and future directions

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Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Development of a Widely Usable Amino Acid Tracer: ⁷⁶Br-α-Methyl-Phenylalanine for Tumor PET Imaging

Effects of Intratumoral Inflammatory Process on ¹⁸F-FDG Uptake: Pathologic and Comparative Study with ¹⁸F-Fluoro-α-Methyltyrosine PET/CT in Oral Squamous Cell Carcinoma