• No relationship between 18F-fluorodeoxyglucose positron emission tomography and expression of Glut-1 and -3 and hexokinase I and II in high-grade glioma.

      Charnley, Natalie; Airley, R; Du Plessis, D; West, Catharine M L; Brock, Cathryn S; Barnett, C; Matthews, Julian C; Symonds, Kirsten; Bottomly, M; Swindell, Ric; et al. (2008-09)
      The purpose of this study was to compare glucose metabolism, measured using 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), with the expression of Glut-1 and -3 and hexokinase I (Hex I) and II in high-grade glioma. The retrospective study involved 27 patients with WHO classification grade III and IV glioma, with either newly diagnosed or recurrent tumours. Patients underwent dynamic and static [18F]FDG-PET to glucose metabolic rate (MRGlu) and standardised uptake value (SUV), respectively. Tumour biopsies were obtained and stained using immunohistochemistry for the expression of Glut-1, -3, Hex I and II. Relationships between variables were studied using Spearman's rank correlation test. Results showed that the expression of Glut-1, Glut-3, Hex I and Hex II varied between and within the tumour samples. The mean of MRGlu was 0.2 (range 0.09-0.25) micromol/min/ml and that of SUV was 4.2 (range 3.2-5.2). There were no significant relationships among the tumour expression of any of the proteins studied with either MRGlu or SUV (p>0.21 for all). In conclusion, the lack of relationship between the immunohistochemical expression of Glut-1, -3, Hex I or II and glucose metabolism measured using [18F]FDG-PET in patients with high-grade glioma may be due to the tissue heterogeneity and presence of necrosis in high-grade tumours.
    • Optimization of the injected activity in dynamic 3D PET: a generalized approach using patient-specific NECs as demonstrated by a series of 15O-H2O scans.

      Walker, Mathew D; Matthews, Julian C; Asselin, Marie-Claude; Saleem, Azeem; Dickinson, Clare; Charnley, Natalie; Julyan, Peter J; Price, Patricia M; Jones, Terry; School of Cancer and Imaging Sciences, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom. (2009-01-30)
    • Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radioisotopes.

      Saleem, Azeem; Aboagye, E O; Matthews, Julian C; Price, Patricia M; Academic Department of Radiation Oncology, Christie Hospital NHS Foundation Trust, Wilmslow Road, and The University of Manchester Wolfson Molecular Imaging Centre, Manchester M20 4BX, UK. azeem.saleem@manchester.ac.uk (2008-04)
      PURPOSE: This study aimed to evaluate the utility of plasma pharmacokinetic analyses of anti-cancer agents from data obtained during positron emission tomography (PET) oncology studies of radiolabelled anti-cancer agents. PATIENTS AND METHODS: Thirteen patients were administered fluorine-18 radiolabelled 5-FU ([(18)F]5-FU) admixed with 5-FU, corresponding to a total 5-FU dose of 380-407 mg/m2 (eight patients) and 1 mg/m2 (five patients). Nine patients received 2.2-19.2 microg/m2 of carbon-11 radiolabelled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide ([11C]DACA) at 1/1,000th of phase I dose, as part of phase 0 microdosing study. Radioactivity of parent drug obtained from arterial blood samples, the injected activity of the radiolabelled drug, and the total dose of injected drug were used to obtain plasma drug concentrations. Plasma pharmacokinetic parameters were estimated using model-dependent and model-independent methods. RESULTS: 5-FU plasma concentrations at therapeutic doses were above the Km and a single compartment kinetic model was best used to fit the kinetics, with a mean half-life of 8.6 min. Clearance and volumes of distribution (Vd) obtained using both model-dependent and model-independent methods were similar. Mean (SE) clearance was 1,421(144), ml min(-1) and 1,319 (119) ml min(-1) and the mean (SE) Vd was 17.3 (1.8) l and 16.3 (1.9) l by the model-independent method and model-dependent methods, respectively. In contrast, with 1 mg/m2, plasma concentrations of 5-FU were less than the Km and a two-compartment model was used to best fit the kinetics, with the mean 5-FU half-life of 6.5 min. The mean (SE) clearances obtained by the model-independent method and model-dependent methods were 3,089 (314) ml min(-1) and 2,225 (200) ml min(-1), respectively and the mean (SE) Vd were 27.9 (7.0) l and 2.3 (0.4) l, by the model independent and dependent methods, respectively. Extrapolation of AUC0-Clast to AUC0-infinity was less than 3% in both these cohort of patients. A two-compartment model with a mean half-life of 42.1 min was used to best fit the kinetics of DACA; considerable extrapolation (mean 26%) was required to obtain AUC0-infinity from AUC0-Clast. Mean (SE) clearance of DACA was 1,920 (269) ml min(-1), with the model-independent method and 1,627 (287) ml min(-1) with the model-dependent method. Similarly, Vd [mean (SE)] of DACA with the model-independent and model-dependent methods were 118 (22) l and 50 (15) l, respectively. CONCLUSIONS: Pharmacokinetic parameters can be estimated with confidence from PET studies for agents given at therapeutic doses, whose half-lives are significantly less than the total sampling time during the scan. Tracer studies performed alone, wherein plasma levels below the Km are expected, may also provide valuable information on drug clearance for the entire range of linear kinetics. However, drugs with half-lives longer than the sampling duration are inappropriate for PET plasma pharmacokinetic evaluation.