Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRgluvaried among different tumor lesions, but mean Vdwas comparable in all lesions. After one course of chemotherapy, mean MRgludecreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vddecreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRgluresponse could be very heterogeneous, even within similar types of metastases. BF and MRgluincreased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRgluchanges separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRgluparameters can be remarkably heterogeneous in patients with multiple lesions

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

Validity of Simplified 3 '-Deoxy-3 '-[F-18]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

Experimentele farmacotherapi