Monitoring Response to Radiotherapy in Human Squamous Cell Cancer Bearing Nude Mice: Comparison of 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG) and 3′-[18F]fluoro-3′-deoxythymidine (FLT)

Objective: The uptake of 3′-[18F]fluoro-3′- deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG). Materials and Methods: Nude mice bearing established human head and neck xenografts (HNX-OE; nu/nu mice) were locally irradiated (three fractions/week; 22 Gy) using a 150-kVp unit. Multiple FDG- and FLT-PET scans were acquired during treatment. Tumor volume was determined regularly, and tissue was analyzed for biomarkers involved in tracer uptake. Results: Both groups revealed a significant decline in tumor volume (P∈<∈0.01) compared to untreated tumors. For FDG as well as for FLT, a significant decline in retention was observed at day 4. For FLT, most significant decline in retention was observed at day 12; whereas, for FDG, this was already noted at day 4. Maximum decline in tumor-to-nontumor ratios (T/NT) for FDG and FLT was 42∈±∈18% and 49∈±∈16% (mean∈± ∈SD), respectively. FLT uptake was higher then that of FDG. For FLT, statistical significant correlations were found for both tumor volume at baseline and at day 29 with T/NT and ΔT/NT. All tumors demonstrated expression of glucose transporter-1, thymidine kinase-1, and hexokinase II. No differences were found for amount of tumor cells and necrosis at the end of treatment. Conclusion: This new experimental in vivo model supports the promise of using FLT-PET, as with FDG-PET, to monitor response to external radiotherapy. This warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy

Reproducibility of quantitative F-18-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography

Positron emission tomography (PET) using F-18-3'-deoxy-3'-fluorothymidine ([F-18]FLT) allows noninvasive monitoring of tumour proliferation. For serial imaging in individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative [F-18]FLT measurements. Nine patients with non-small-cell lung cancer (NSCLC) and six with head-and-neck cancer (HNC) underwent [F-18]FLT PET twice within 7 days prior to therapy. The maximum pixel value (SUVmax) and a threshold defined volume (SUV41%) were defined for all delineated lesions. The plasma to tumour transfer constant (K-i) was estimated using both Patlak graphical analysis and nonlinear regression (NLR). NLR was also used to estimate k(3), which, at least in theory, selectively reflects thymidine kinase 1 activity. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. All primary tumours and > 90% of clinically suspected locoregional metastases could be delineated. In total, 24 lesions were defined. NLR-derived K-i, Patlak-derived K-i, SUV41% and SUVmax showed excellent reproducibility with ICCs of 0.92, 0.95, 0.98 and 0.93, and SDs of 16%, 12%, 7% and 11%, respectively. Reproducibility was poor for k(3) with an ICC of 0.43 and SD of 38%. Quantitative [F-18]FLT measurements are reproducible in both NSCLC and HNC patients. When monitoring response in individual patients, changes of more than 15% in SUV41%, 20-25% in SUVmax and Patlak-derived K-i, and 32% in NLR3k-derived K-i are likely to represent treatment effect

Matching PET and CT scans of the head and neck area: Development of method and validation

Positron emission tomography (PET) provides important information on tumor biology, but lacks detailed anatomical information. Our aim in the present study was to develop and validate an automatic registration method for matching PET and CT scans of the head and neck. Three difficulties in achieving this goal are (1) nonrigid motions of the neck can hamper the use of automatic ridged body transformations; (2) emission scans contain too little anatomical information to apply standard image fusion methods; and (3) no objective way exists to quantify the quality of the match results. These problems are solved as follows: accurate and reproducible positioning of the patient was achieved by using a radiotherapy treatment mask. The proposed method makes use of the transmission rather than the emission scan. To obtain sufficient (anatomical) information for matching, two bed positions for the transmission scan were included in the protocol. A mutual information-based algorithm was used as a registration technique. PET and CT data were obtained in seven patients. Each patient had two CT scans and one PET scan. The datasets were used to estimate the consistency by matching PET to CT1, CT1, to CT2, and CT2 to PET using the full circle consistency test. It was found that using our method, consistency could be obtained of 4 mm and 1.3° on average. The PET voxels used for registration were 5.15 mm, so the errors compared quite favorably with the voxel size. Cropping the images (removing the scanner bed from images) did not improve the consistency of the algorithm. The transmission scan, however, could potentially be reduced to a single position using this approach. In conclusion, the represented algorithm and validation technique has several features that are attractive from both theoretical and practical point of view, it is a user-independent, automatic validation technique for matching CT and PET scans of the head and neck, which gives the opportunity to compare different image enhancements

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015–2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios