Anthony F. Shields

Bio: Anthony F. Shields is an academic researcher from Wayne State University. The author has contributed to research in topics: Thymidine & Positron emission tomography. The author has an hindex of 16, co-authored 16 publications receiving 2778 citations. Previous affiliations of Anthony F. Shields include Harper University Hospital.

Imaging proliferation in vivo with [F-18]FLT and positron emission tomography.

Abstract: Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.

Imaging of Cell Proliferation: Status and Prospects

Abstract: Increased cellular proliferation is an integral part of the cancer phenotype. Several in vitro assays have been developed to measure the rate of tumor growth, but these require biopsies, which are particularly difficult to obtain over time and in different areas of the body in patients with multiple metastatic lesions. Most of the effort to develop imaging methods to noninvasively measure the rate of tumor cell proliferation has focused on the use of PET in conjunction with tracers for the thymidine salvage pathway of DNA synthesis, because thymidine contains the only pyrimidine or purine base that is unique to DNA. Imaging with 11C-thymidine has been tested for detecting tumors and tracking their response to therapy in animals and patients. Its major limitations are the short half-life of 11C and the rapid catabolism of thymidine after injection. These limitations led to the development of analogs that are resistant to degradation and can be labeled with radionuclides more conducive to routine clinical use, such as 18F. At this point, the thymidine analogs that have been studied the most are 3'-deoxy-3'-fluorothymidine (FLT) and 1-(2'-deoxy-2'-fluoro-1-beta-d-arabinofuranosyl)-thymine (FMAU). Both are resistant to degradation and track the DNA synthesis pathway. FLT is phosphorylated by thymidine kinase 1, thus being retained in proliferating cells. It is incorporated by the normal proliferating marrow and is glucuronidated in the liver. FMAU can be incorporated into DNA after phosphorylation but shows less marrow uptake. It shows high uptake in the normal heart, kidneys, and liver, in part because of the role of mitochondrial thymidine kinase 2. Early clinical data for 18F-FLT demonstrated that its uptake correlates well with in vitro measures of proliferation. Although 18F-FLT can be used to detect tumors, its tumor-to-normal tissue contrast is generally lower than that of 18F-FDG in most cancers outside the brain. The most promising use for thymidine and its analogs is in monitoring tumor treatment response, as demonstrated in animal studies and pilot human trials. Further work is needed to determine the optimal tracer(s) and timing of imaging after treatment.

Carbon-11-Thymidine and FDG to Measure Therapy Response

Abstract: UNLABELLED This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.

Molecular imaging in living subjects: seeing fundamental biological processes in a new light

Abstract: References http://genesdev.cshlp.org/content/17/5/545.full.html#related-urls Article cited in: http://genesdev.cshlp.org/content/17/5/545.full.html#ref-list-1 This article cites 228 articles, 79 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article sign up in the box at the Collections Topic (33 articles) Molecular Physiology and Metabolism • (98 articles) Cancer and Disease Models • Articles on similar topics can be found in the following collections

Molecular imaging of cancer with positron emission tomography.

Abstract: The imaging of specific molecular targets that are associated with cancer should allow earlier diagnosis and better management of oncology patients. Positron emission tomography (PET) is a highly sensitive non-invasive technology that is ideally suited for pre-clinical and clinical imaging of cancer biology, in contrast to anatomical approaches. By using radiolabelled tracers, which are injected in non-pharmacological doses, three-dimensional images can be reconstructed by a computer to show the concentration and location(s) of the tracer of interest. PET should become increasingly important in cancer imaging in the next decade.

Imaging proliferation in vivo with [F-18]FLT and positron emission tomography.

Abstract: Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.

Molecular imaging in drug development

Abstract: Molecular imaging, which can allow the non-invasive monitoring of biological processes in living subjects, has the potential to enhance understanding of disease and drug activity in both preclinical and clinical drug studies, aiding effective translational research. Gambhir and colleagues review the applications of molecular imaging in drug development, and discuss challenges that need to be addressed to optimize its utility.

Simultaneous PET-MRI: a new approach for functional and morphological imaging

Abstract: Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.