Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I–III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; P<0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I–III NSCLC

Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography

Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure-activity relationship study was carried out. Positron Emission Tomography (PET) using (18)F-L-1-(2′-deoxy-2′-FluoroArabinofuranosyl) Cytosine ((18)F-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC(50) = ∼1 – 12 nM) using the (18)F-L-FAC PET pharmacodynamic assay identified compounds demonstrating superior in vivo efficacy

A comparative study of 11C-choline PET and [18F]fluorodeoxyglucose PET in the evaluation of lung cancer

The purpose of this study was to compare the diagnostic value of 11C-choline positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET imaging in the detection of primary lung cancer and mediastinal lymph node metastases. Seventeen patients with histologically proven primary lung cancer were examined with both 11C-choline and FDG PET within a week of each study. Lung cancers were analysed visually and semiquantitatively using the ratio of tumour-to-normal radioactivity (T/N ratio) and standardized uptake value (SUV). Mediastinal lymph node metastases were analysed visually. Although both techniques delineated focal lesions with an increase intracer accumulation in 13 patients, FDG PET identified three additional patients in whom 11C-choline PET did not visualize any lesion. In the detection of lung cancer <2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than 11C-choline PET (four of seven, 57.1%). THe T/N ratio and SUV were significantly higher with FDG PET (T/N ratio, 7.43 6.22, SUV, 4.05 3.05) than these were with 11C-choline PET (T/N ratio, 2.93 1.19, SUV, 2.93 0.79)(p<0.001). Tｈere was a significant positive correlation between tha T/N ratios and SUVs of FDG and 11C-choline. In the assessment of mediastinal lymph node involvement, FDG PET detected lymph node metastases in two patients who were negative on 11C-choline PET, whereas both techniques could not detect tumour involvement in one patient, Both techniques have clinical value for the non-invasive detection of primary lung cancer that is 2 cm or greater in size. However, FDG PET is superior to 11C-choline PET in the detection of lung cancer that is less than 2 cm in diameter and in mediastinal lymph node metastases