[F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: clinical outcomes and patterns of failure.

Purpose: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme.

Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography.

Background: Numerous knockout mouse studies have revealed that P-glycoprotein (P-gp) significantly limits drug distribution across the mouse blood-brain barrier (BBB). To determine the importance of P-gp at the human BBB, we developed a state-of-the-art, noninvasive, quantitative imaging technique to measure P-gp activity by use of carbon 11-labeled verapamil as the P-gp substrate and cyclosporine (INN, ciclosporin) as the P-gp inhibitor.

Methods: In brief, 11C-verapamil (approximately 0.

Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development.

2-[(18)F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care.

Evolving role of positron emission tomography in breast cancer imaging.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used for detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy.

Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies.

Unlabelled: We present a method to measure the regional rate of cellular proliferation using a positron-emitting analog of thymidine (TdR) for human imaging studies. The method is based on the use of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) to estimate the flux of TdR through the exogenous pathway. The model reflects the retention of FLT-monophosphate (FLTMP), which is generated by the phosphorylation of FLT by thymidine kinase 1 (TK1), the initial step in the exogenous pathway.

Kinetic analysis of 3'-deoxy-3'-fluorothymidine PET studies: validation studies in patients with lung cancer.

Unlabelled: Assessing cellular proliferation provides a direct method to measure the in vivo growth of cancer. We evaluated the application of a model of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) kinetics described in a companion report to the analysis of FLT PET image data in lung cancer patients. Compartmental model analysis was performed to estimate the overall flux constants (K(FLT)) for FLT phosphorylation in tumor, bone marrow, and muscle.

PET imaging of cellular proliferation.

PET cellular proliferation imaging has its roots in a long history of in vitro cellular proliferation studies to characterize cancer and in the understanding of the biology of thymidine incorporation into DNA gained from these studies. PET imaging represents the logical translation of the in vitro work to measure in vivo tumor proliferation. Preclinical studies of [11C]-thymidine and other PET-labeled thymidine analogues set the stage for early clinical studies that provided very promising results.

Residual tumor uptake of [99mTc]-sestamibi after neoadjuvant chemotherapy for locally advanced breast carcinoma predicts survival.

Background: Studies utilizing serial [99mTc]-sestamibi (MIBI) scintimammography have reported accurate prediction of tumor response in patients with locally advanced breast carcinoma (LABC) undergoing neoadjuvant chemotherapy. The pathologic response of LABC to presurgical treatment regimens is a prognostic indicator of survival. The authors tested whether MIBI uptake posttherapy predicted survival.

18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy.

Unlabelled: The aim of this study was to characterize the biologic response of locally advanced breast cancer (LABC) to chemotherapy using (15)O-water-derived blood flow measurements and (18)F-FDG-derived glucose metabolism rate parameters.

Methods: Thirty-five LABC patients underwent PET with (15)O-water and (18)F-FDG before neoadjuvant chemotherapy and 2 mo after the initiation of treatment. Kinetic analysis for (15)O-water was performed using a single tissue compartment model to calculate blood flow; a 2-tissue compartment model was used to estimate (18)F-FDG rate parameters K(1), k(2), k(3), and the flux constant, K(i).

Combined use of MRI and PET to monitor response and assess residual disease for locally advanced breast cancer treated with neoadjuvant chemotherapy.

Rationale And Objectives: The purpose of the study was to evaluate the hypothesis that magnetic resonance imaging (MRI) and positron emission tomography (PET) are complementary and valuable in monitoring response and assessing residual disease of locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. We sought to determine if the combination of the two modalities was more accurate than either alone and could provide better guidance in patient management.

Materials And Methods: Sixteen lesions in 15 women with LABC were evaluated with MRI, PET, and clinical breast examination (CBE) before and after neoadjuvant chemotherapy.

18F-FDG PET of gliomas at delayed intervals: improved distinction between tumor and normal gray matter.

Unlabelled: We hypothesized that delineation of gliomas from gray matter with 18F-FDG PET could be improved by extending the interval between 18F-FDG administration and PET data acquisition. The purposes of this study were, first, to analyze standard and delayed 18F-FDG PET images visually and quantitatively to determine whether definition of tumor improved at later imaging times and, second, to investigate the dynamics of model-derived kinetic rate constants, particularly k4.

Methods: Nineteen adult patients with supratentorial gliomas were imaged from 0 to 90 min and once or twice later at 180-480 min after injection.

Comparison of different quantitative approaches to 18F-fluoride PET scans.

Unlabelled: The aim of this study was to evaluate the relationship between 18F-fluoride bone metabolic measures obtained by nonlinear regression (NLR), Patlak analysis, and standardized uptake value (SUV) for a wide range of normal and pathologic bone conditions. In patients imaged twice, changes in metabolic rates were determined using the different quantitation methods.

Methods: In 33 patients 2-51 mo after resection of a bone tumor of the limbs, a total of 42 dynamic PET scans were performed after injection of 250-350 MBq 18F-fluoride.

Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).

The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases.

Impact of FDG PET on defining the extent of disease and on the treatment of patients with recurrent or metastatic breast cancer.

Objective: Our aim was to evaluate the impact of FDG PET on defining the extent of disease and on the treatment of patients with advanced breast cancer.

Materials And Methods: The medical records of 125 consecutive patients with recurrent or metastatic breast cancer referred for FDG PET from January 1998 through May 2002 were retrospectively reviewed. The rationale for FDG PET referral and the impact of FDG PET on subsequent treatment decisions for patients were determined by chart review.

Current and future uses of positron emission tomography in breast cancer imaging.

Positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) has been used for the detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy.

Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging.

Purpose: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake.

Positron emission tomography imaging of brain tumors.

Energy metabolism and amino acid transport and incorporation are important components of the pathophysiology of gliomas, about which molecular imaging is providing regional biologic information that is useful to clinical practice. Imaging hypoxia is straightforward and proliferation imaging with FLT shows significant promise. Neither has been exploited thoroughly enough to allow judgement of their potential benefit to the practice of neuro-oncology.

Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy.

Unlabelled: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we performed serial measurements of blood flow and glucose metabolism in LABC patients over the course of neoadjuvant chemotherapy and compared measurements with response.

18F-Fluorothymidine radiation dosimetry in human PET imaging studies.

Unlabelled: 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET imaging agent that shows promise for studying cellular proliferation in human cancers. FLT is a nucleoside analog that enters cells and is phosphorylated by human thymidine kinase 1, but the 3' substitution prevents further incorporation into DNA. We estimated the radiation dosimetry for this tracer from data gathered in patient studies.

Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: compartmental model investigation and mathematical analysis.

Unlabelled: 2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood-brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors.

Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estirmine whether it can distinguish between thymidine transport and retention.

Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: preliminary patient results.

Unlabelled: 2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. Kinetic analysis of dynamic TdR images was performed to estimate the rate of thymidine transport (K1t) and thymidine flux (KTdR) into brain tumors and normal brain. These estimates were compared to MRI and pathologic results.

SUV varies with time after injection in (18)F-FDG PET of breast cancer: characterization and method to adjust for time differences.

Unlabelled: The purpose of this study was to measure how (18)F-FDG PET standardized uptake values (SUVs) change over time in breast cancer and to examine the feasibility of a method to adjust for modest variations in the time of uptake measurement experienced in clinical practice.

Methods: (18)F-FDG PET was performed as 60-min dynamic imaging with an additional image acquired at approximately 75 min after injection. For 20 newly diagnosed, untreated, locally advanced breast cancer patients, both the maximum SUV and the average SUV within the lesion were calculated with and without correction for blood glucose concentration.