Differential Diagnosis between Low-Grade and High-Grade Astrocytoma Using System A Amino Acid Transport PET Imaging with C-11-MeAIB: A Comparison Study with C-11-Methionine PET Imaging.

Introductions: [N-methyl-C-11]α-Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET. Methods: Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma (n=12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy (n=19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue (T/N) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated. Results: In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group (p < 0.005), and the T/N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group (p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group (p < 0.005), and the T/N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group (n.s.). For the analysis using the T/N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T/N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET (p < 0.01). Conclusions: MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T/N ratio. Clinical trial registration: This trial was registered with UMIN000032498.

Intra- and inter-observer agreement in the visual interpretation of interim 18F-FDG PET/CT in malignant lymphoma: influence of clinical information.

Background Interim PET/CT is widely performed in lymphoma patients in clinical practice and clinical trials. Visual assessment using a 5-point scale is proposed for PET/CT interpretation, but intra- and inter-observer variation is not fully investigated. Purpose To investigate intra- and inter-observer variations in the reporting of interim positron emission tomography/computed tomography (PET/CT) in lymphoma patients, and the influence of clinical information on the interpretation. Material and Methods Three expert readers from different institutions interpreted interim PET/CT images of 42 consecutive patients with malignant lymphoma twice, with and without clinical information. The intra- and inter-observer agreements were calculated using the kappa statistic on a patient and a region basis. Results On a patient basis, intra-observer agreement, inter-observer agreement without information, and inter-observer agreement with information were within the ranges 0.48-0.62, 0.51-0.62, and 0.42-0.76, respectively. In the evaluation of lymph nodes, intra-observer agreement, inter-observer agreement without information, and inter-observer agreement with information were within the ranges 0.78-0.92, 0.80-0.82, and 0.77-0.83, respectively. Observer agreements were in almost perfect to substantial agreement categories for most lymphatic organs, but were generally low for the other organs. Conclusion The intra- and inter-observer agreements in evaluating interim PET/CT were relatively low for extranodal lesions, but they were substantial to almost perfect when interpreting nodal regions in malignant lymphoma, irrespective of the provision of clinical information, although memory at the first interpretation might have affected the intra-observer results.

(11)C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with (18)F-fluorodeoxyglucose PET.

OBJECTIVE: α-N-methyl-(11)C-methylaminoisobutyric acid ((11)C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET. METHODS: Thirty-four men (age range 57-77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer. RESULTS: Mean value of SUVmax of (11)C-MeAIB PET and (18)F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55-9.57) and 3.88 (±2.85, range; 2.04-14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality. CONCLUSIONS: MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than (11)C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.

Increased bone marrow uptake of 18F-FDG in leukemia patients: preliminary findings.

The aim of this retrospective study was to evaluate the characteristics of increased bone marrow uptake of 18F-FDG in patients with leukemia who underwent whole-body 18F-FDG PET/CT. The 18F-FDG PET/CT images of 9 patients with histologically proven leukemia were reviewed. The accumulation of 18F-FDG in the bone marrow was evaluated, and was compared with histological subtype, clinical course, and hematological findings. Nine patients (4 males, 5 females; age range, 5-58 years) had increased bone marrow uptake of 18F-FDG, including 6 patients with acute lymphoblastic leukemia, 1 with acute myeloid leukemia, 1 with chronic myeloid leukemia, and 1 with mature B cell neoplasm. Bone marrow uptake was generally diffuse but focal or inhomogeneous uptake was common, especially in the upper and lower extremities. Patients with increased bone marrow uptake of 18F-FDG commonly complained of fever and bone pain. No correlations between 18F-FDG uptake and peripheral blood findings were observed. Patients with leukemia may have increased bone marrow uptake of 18F-FDG on PET/CT, possibly reflecting leukemic cell activity. Leukemia can be included in the differential diagnosis when increased bone marrow uptake of 18F-FDG is observed.