Tomohiro Ishikita

PET and PET/CT using 18F-FDG in the diagnosis and management of cancer patients

Positron emission tomography (PET) using 2-18F-fluoro-2-deoxy-D-glucose (FDG), a radioactive derivative of glucose, is an advanced imaging tool, based on the increased glucose consumption of cancer cells. FDG-PET provides information that is not obtainable with other imaging modalities, and is very effective in the diagnosis and management of patients with various types of cancers. However, there are some limitations, such as low FDG uptake in some cancers, substantial FDG uptake in inflammatory cells, and the lack of anatomical information and poor imaging quality of PET. A recently developed integrated PET/computed tomography (CT) system, which combines a PET camera and CT scanner in a single session, has overcome these drawbacks by providing both anatomical and functional imaging at the same position. PET and/or PET/CT using FDG is clinically useful in the detection of cancer, the differentiation of malignant and benign lesions, the staging of cancer before therapy, and the assessment of cancer therapy, as well as for determining the recurrence after therapy of most cancers, including lung cancer, gastrointestinal cancer, breast cancer, and malignant lymphoma. PET/CT has become the new standard approach to imaging in the diagnosis and management of many cancer patients.

Present role and future prospects of positron emission tomography in clinical oncology

Positron emission tomography (PET) has emerged as a significant molecular imaging technique in clinical oncology and cancer research. PET with 18F‐fluorodeoxyglucose (18F‐FDG) demonstrates elevated glucose consumption by tumor cells, and is used clinically for the accurate staging and restaging of cancer, planning of radiotherapy, and predicting response or lack of response in the early stages of treatment. Combined PET and computed tomography (PET‐CT) provides both functional and morphological information of the disease to allow accurate diagnosis of cancer. PET with new radiotracers such as protein synthesis markers and proliferation markers, as well as hypoxia and receptor‐binding agents, will offer patient‐specific images in order to yield tailored diagnostic and prognostic information. (Cancer Sci 2006; 97: 1291–1297)

Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer

L‐[3‐18F]‐α‐methyltyrosine (18F‐FMT) is an amino‐acid tracer for positron‐emission tomography (PET). We have conducted a clinicopathologic study to elucidate the correlation of angiogenesis with 18F‐FMT and 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) uptake in patients with non‐small cell lung cancer (NSCLC). Thirty‐seven NSCLC patients were enrolled in this study, and two PET studies with 18F‐FMT and 18F‐FDG were performed. Uptake of PET tracers was evaluated with standardized uptake value. Vascular endothelial growth factor (VEGF), CD31, CD34, L‐type amino acid transporter 1 (LAT1) and Ki‐67 labeling index of the resected tumors were analyzed by immunohistochemical staining, and correlated with the clinicopathologic variables and the uptake of PET tracers. The median VEGF rate was 45% (range, 10–78%). High expression was seen in 30 patients (81%, 30/37). VEGF expression was statistically associated with progressively growing microvessel count. VEGF showed a correlation with LAT1 expression (P = 0.04) and Ki‐67 labeling index (P = 0.01). However, it showed no correlation with age, gender, disease stage, tumor size, and histology. Microvessel density (MVD) showed no correlation with any parameters. 18F‐FMT and 18F‐FDG uptake correlated significantly with VEGF (P < 0.0001, P = 0.026, respectively), whereas the correlation of 18F‐FMT and VEGF was more meaningful. The present study demonstrated that the metabolic activity of primary tumors as evaluated by PET study with 18F‐FMT and 18F‐FDG is related to tumor angiogenesis and the proliferative activity in NSCLC. (Cancer Sci 2009; 100: 753–758)

Evaluation of thoracic tumors with 18 F-FMT and 18 F-FDG PET-CT: A clinicopathological study

L‐[3‐18F]‐α‐methyltyrosine (18F‐FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET‐CT with 18F‐FMT provides additional information for the preoperative diagnostic workup as compared with 18F‐FDG PET. PET‐CT studies with 18F‐FMT and 18F‐FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L‐type amino acid transporter 1 (LAT1), CD98, Ki‐67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, 18F‐FMT PET exhibited a sensitivity of 84% whereas the sensitivity for 18F‐FDG PET was 89% (p = 0.736). 18F‐FMT PET‐CT and 18F‐FDG PET‐CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). 18F‐FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of 18F‐FMT PET for diagnosing thoracic tumors was higher than that of 18F‐FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer.

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

Objectives: To comparel-3-[18F]-fluoro-α-methyltyrosine (FMT)-positron emission tomography (PET) and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET in the differential diagnosis of maxillofacial tumors.Methods: This study included 36 patients (16 males, 20 females; 31–90 years old) with untreated malignant tumors (34 squamous cell carcinoma, one mucoepidermoid carcinoma, one rhabdomyosarcoma) and seven patients (five males, two females; 32–81 years old) with benign lesions. In all patients, both FMT-PET and FDG-PET were performed within two weeks before biopsy or treatment of the lesions. To evaluate the diagnostic usefulness of FMT-PET and FDG-PET, visual interpretation and semiquantitative analysis were performed. PET images were rated according to the contrast of tumor uptake as compared with background, and were statistically analyzed. As a semiquantitative analysis, standardized uptake values (SUV) of the primary tumors were measured, and the SUV data were analyzed using receiver operating characteristic (ROC) curves.Results: The mean SUV of the malignant lesions were significantly higher than those of the benign lesions in both FMT-PET (2.62±1.58 vs. 1.20±0.30, p<0.01) and FDG-PET (9.17±5.06 vs. 3.14±1.34, p<0.01). A positive correlation (r=0.567, p<0.0001, n=46) was noted between FMT and FDG. ROC analysis revealed that there was no statistically significant difference in SUVs between FMT and FDG for differentiating malignant tumors. In 27 of 36 patients, FMT-PET had better contrast of malignant tumor visualization to the surrounding normal structures by visual assessment (p<0.005, binomial proportion test).Conclusions: Differential diagnosis of FMT-PET based on the uptake in maxillofacial tumors is equivalent to FDG-PET. However, the contrast of FMT uptake between maxillofacial tumors and the surrounding normal structures is higher than that of FDG, indicating the possibility of accurate diagnosis of maxillofacial tumors by FMT-PET.

Clinicopathological presentation of varying 18F-FDG uptake and expression of glucose transporter 1 and hexokinase II in cases of hepatocellular carcinoma and cholangiocellular carcinoma

We report the results of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and immunohistochemical staining of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in patients with hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) to observe the variation in 18F-FDG uptake and variation in expression of Glut-1 and HK-II in these hepatic tumors. In the case of HCC, moderate 18F-FDG uptake and strong expression of HK-II were detected, whereas Glut-1 was not expressed. Conversely, CCC showed high 18F-FDG uptake and increased expression of Glut-1 but HK-II was not expressed. The variation in the 18F-FDG uptake and expression of Glut 1 and HK-II in HCC and CCC might be owing to the difference in origin and the different mechanisms involved in glucose uptake, rate of glucose transporters, and hexokinase activity involved in the glycolytic pathway.

Pulmonary artery intimal sarcoma: the role of 18 F-fluorodeoxyglucose positron emission tomography in monitoring response to treatment

We report the case of 58-year-old man with pulmonary artery intimal sarcoma. He initially presented with cough, right-sided chest pain, and shortness of breath. Although the diagnosis of pulmonary embolism had been considered, chest radiograph and pulmonary perfusion scintigraphy showed a mass in the right hilum and no perfusion in the right lung. 18F-fluorodeoxyglucose positron emission computed tomography (FDGPET) showed increased FDG uptake in the mass obstructing the right pulmonary artery. Fine-needle biopsy revealed a pathological diagnosis of pulmonary artery intimal sarcoma. The patient was successfully treated with radiotherapy and adjuvant chemotherapy. FDG-PET was used for monitoring the response to therapy.