Browsing by Subject "Neoplasms"
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Item A mechanistic analysis of DNA vaccine-induced tumor immunity against the viral oncoprotein simian virus 40 large tumor antigen(2012-05) Aldrich, Joel; Bright, Robert K.; Jumper, Cynthia A.; Winn, Richard; Brackee, Gordon; Colmer-Hamood, Jane; Sutton, VictoriaAs cancer progresses toward the leading cause of death in the United States, biomedical research has become increasingly invested in the study of vaccines as potentiators of tumor immunity. Unlike current treatments for malignant disease, active immunotherapy has the potential to establish a specific, long-lasting anti-tumor response in the absence of debilitating side effects. In this study, we aim to characterize the immunological mechanisms of tumor immunity in BALB/c mice following vaccination with plasmid DNA, designated pCMV-Tag, that expresses as a transgene, a tumor specific antigen (Tag) from simian virus 40 (SV40). Briefly, BALB/c mice were immunized with pCMV-Tag or a control plasmid DNA preparation and subsequently challenged with a syngeneic murine fibroblast tumor cell line that expresses SV40 Tag in an experimental pulmonary metastasis model of malignant disease. Induction phase and effector phase-depletions of T lymphocytes and NK cells were performed in vivo to assess the relative importance of these cell types in the elicitation of tumor immunity. Additionally, gamma interferon (IFN-γ) neutralization experiments were conducted in vivo to examine the required activity of this cytokine at different stages of the immune response. An evaluation of anti-tumor immunity was carried out by monitoring the formation of lung tumor foci within the experimental pulmonary metastasis scenario followed by the evaluation of SV40 Tag specific immune responses. Our results indicate CD4+ T cells are critical mediators of the anti-tumor immune response, while CD8+ T cells and NK cells execute an important overlapping function within the immune effector phase. Studies of the specific cytokine environment show that vaccination with pCMV-Tag generates T cells that produce IFN-γ in vitro, which is a required component of the induction phase of the anti-tumor immune response. Of note, studies of the humoral immune response indicate that complete protection from tumor development precedes antibody production, and that the distribution of SV40 Tag-specific IgG sub-isotypes is consistent with a mixed Th1/Th2 immune response. Our findings provide insight into the general mechanisms of DNA vaccine-induced immunity against tumor-associated antigens, and have implications for the development of novel strategies to treat malignancies that express definable antigens that can be targeted through active vaccination.Item Anti-Angiogenic Therapy in Non-Small Cell Lung Cancer: Characterizing a New Therapy and Investigating Potential Mechanisms of Resistance(2012-07-20) Sullivan, Laura Anne; Brekken, Rolf A.Angiogenesis is the development of blood vessels from a pre-existing vascular network. This process is essential during growth, development and wound healing and plays a critical role in the growth and progression of cancer. Initial tumor size is restricted by the diffusion capacity of oxygen and nutrients from surrounding blood vessels. Therefore, to progress beyond a volume of several millimeters, a tumor must stimulate angiogenesis to generate a vascular network that will supply the tumor with the necessary blood, oxygen and nutrients that will allow for continued growth, invasion and metastasis. Over forty years ago, Judah Folkman hypothesized that targeting tumor angiogenesis would be beneficial for cancer patients. One of the first targets for this new class of drugs was vascular endothelial growth factor (VEGF) a predominant mediator of physiological and pathological angiogenesis. Bevacizumab (Avastin®, Genentech/Roche), a humanized monoclonal antibody that recognizes human VEGF and blocks VEGF from binding to VEGF receptor (VEGFR) 1 and 2, was the first anti-angiogenic drug approved by the United States Food and Drug Administration for the treatment of cancer and remains the gold standard for this class of therapeutics. The Brekken laboratory, in collaborations with Peregrine Pharmaceuticals and Affitech A/S has generated a fully human monoclonal antibody, r84 that recognizes mouse and human VEGF and blocks VEGF binding only to VEGFR2. The data presented in the first half of this dissertation demonstrate the specificity of r84 for VEGF in vitro and in vivo, the efficacy of r84 to control tumor growth and the superior safety profile of r84 as compared to bevacizumab. Although anti-angiogenic therapy was highly anticipated to have great success in patients, overall results have been somewhat disappointing with modest improvements in patient progression free survival and few improvements to overall survival. In addition, with the expanding use of anti-angiogenic drugs such as bevacizumab and a host of receptor tyrosine kinase inhibitors in the clinic, it is becoming increasingly apparent that not all tumors respond or maintain sensitivity to treatment. Therefore, it is increasingly important to identify mechanisms of resistance to anti-angiogenic therapy so that new drug targets can be identified and/or patients can be appropriately screened for markers that can predict for resistance or sensitivity to anti-angiogenic therapy de novo. Non-small cell lung cancer (NSCLC), the most common form of lung cancer, claims the most new diagnoses and cancer-related deaths than any other cancer worldwide and the therapeutic options currently available for this disease, including bevacizumab have done little to change this statistic. The latter half of this thesis focuses on the in vivo screening of human NSCLC cell lines to identify mechanisms of resistance to the anti-angiogenic monoclonal antibodies bevacizumab and r84 in non-small cell lung cancer.Item Attachment Influences within a Gynecologic Cancer Population(2012-08-31) Adams, Cassandra Leigh; Evans, Harry Monty, Ph.D.Despite significant levels of distress and demonstrated benefits of psychosocial intervention, few women diagnosed with gynecologic cancers utilize psychosocial resources. Research indicates adult attachment style and perception of social support impact distress. However, relationships between these variables are poorly understood. Participants completed measures of distress, adult attachment style, and perception of social support and provided information regarding self-reported openness to psychosocial services and barriers to using those services. Our analyses identified significant relationships between adult attachment dimensions, distress, perceived social support, and openness to and use of psychosocial services. Distress was significantly associated with openness to and use of psychiatric medication. Perceived social support demonstrated significant mediation effects between attachment anxiety and distress. Similarly, perceived social support demonstrated significant mediation effects in the relationship of elevated depression and high attachment avoidance to use of psychiatric medication. However, significant study limitations may be assumed to have negatively impacted the ability to draw meaningful conclusions from the data. Future research would benefit from further examination of the relationships among adult attachment, distress, perceived social support, and openness to and use of psychosocial services. Clearer understanding the nature of these relationships could guide care providers in being able to more effectively provide services to women who are experiencing significant distress but fail to access services. More effective provision of services and subsequent reduction in distress would likely improve health outcomes.Item Development of Novel Cancer Immunotherapeutics Utilizing Cell-Targeting Peptides(2013-01-17) Diaz, Tracy Montie; Brown,Kathlynn Corrine, Ph.D.Cancer immunotherapy is an emerging treatment option that offers high tumor specificity and efficacy. Immune therapies for cancer can be divided into two main types: active and passive. Active therapy strives to achieve a long term protective immunity against a tumor antigen while passive therapy supplies exogenous immunological reagents for anti-tumor effector functions. Both immunotherapies can be improved by utilizing cell targeting peptides. Dendritic Cell Targeting Peptides: Cancer vaccines can elicit immune responses against tumor antigens. Antigen-pulsed in vitro matured dendritic cells (DCs) are used for higher efficacy. However, this method does not provide a significant therapeutic immune response. A more robust anti-tumor immune response could potentially be achieved through in vivo DC targeting of tumor antigens. Through phage-displayed peptide library panning protocol, four different DC-targeting phage clones were isolated. Of those, XS52.1 and XS52.3 bind specifically to the XS52 immature dendritic cells. The XS52.3 phage clone also binds bone-marrow dendritic cells (BMDCs) from Balb/c and C57BL/J6 mice. Each phage clone elicited heightened anti-phage antibody production in both mouse strains. Potential future studies will determine if these peptides can be used to target antigen to DCs for in vivo cancer vaccines. Peptide-Antibody Targeting: Monoclonal antibodies directed against tumor antigens have been successful in clinics, but problems remain with identifying and validating new targets. Modification of the antibody scaffold for distinct applications can also be problematic. Using our phage display panning protocol, we have identified ligands of high affinity and specificity against a panel of human non-small cell lung cancer (NSCLC) cell lines. Furthermore, these peptide-targeting ligands can be chemically synthesized and easily modified for different uses. In my studies, synthetic-peptide ligands have been used to redirect antibody targeting by using biotinylated-tetrameric peptides and anti-biotin antibodies. These results suggest that peptide-antibody conjugates utilizing isolated peptides can be used to redirect antibody targeting. This methodology would increase the antibody repertoire available for therapy.Item Discovery and characterization of novel chemical inhibitors of Wnt ligand production with implications for anti-cancer therapy(2012-07-20) Dodge, Michael E.; Lum, Lawrence Dr.The widespread and indispensable nature of Wnt morphogens during early development has long been a focal point of embryogenesis research. More recently, pathway activation has been uncovered in adult stem cell niches and cancers arising from associated tissues. Consequently, interest has shifted towards achieving chemically based control over aberrant pathway responses, with the ultimate goal of creating therapeutic utility. To this end our laboratory screened a diverse 200K compound library using cell based transcriptional reporters and uncovered several classes of small molecules that modulate distinct Wnt regulatory nodes. One class in particular, termed IWP (Inhibitor of Wnt Production), represents the first specific chemical inhibitors of a Membrane Bound O-Acyltransferase family member: Porcupine. Herein we postulate that IWPs function by binding to and disrupting Porcupine?s active site, preventing subsequent acylation of Wnt ligands necessary for downstream pathway activation. Further SAR studies reveal first generation IWP lead structures to be superior at this task in vitro, with even modest structural changes negatively impacting compound activity. Finally, we propose that due to Porcupine?s upstream position within the Wnt pathway, IWP administration has the potential to disrupt oncogenic contributions made by recently uncovered non-canonical Wnt signaling events. Together these findings advance our understanding of Wnt chemical tractability with long-term implications for targeted therapies. [Keywords: Wnt pathway, porcupine, IWP, Wnt7b, MBOAT, lung cancer, acyltransferase, chemical inhibitor]Item Dynamic Magnetic Resonance Imaging for Tumor Prognosis(2006-08-11) Jiang, Lan; Mason, Ralph P.Breast and prostate cancers are the most common non-smoking cancers among American women and men. Radiotherapy and chemotherapy in conjunction with surgery are the most common treatment protocols in the clinic. However, a lot of experimental and clinical studies have shown that tumor hypoxia and the microcirculation play a very important role in cancer progression and therapy. There is strong evidence that hypoxic cells are one of the major reasons for failure to control tumors with conventional radiotherapy and chemotherapy. Several approaches (hyperthermia and carbogen inhalation), which improve tumor oxygenation during radiotherapy and chemotherapy, have been used in clinical trials. There is increasing demand for tumor prognostic information in the clinical setting. So far, increasing clinical data have indicated that poorly oxygenated tumors have poor prognosis. To better understand the underlying tumor physiological mechanisms, it is very important to develop novel non-invasive approaches to accurately assess tumor microcirculation and oxygenation for further therapy planning. However, these parameters have been extremely difficult to assess in routine clinical practice and have therefore not been easily integrated in to general patient care. With development of MRI the non-invasive technique, BOLD (Blood Oxygenation Level Dependent) contrast MRI, has been widely used for neuroscience research to detect brain activations. Because deoxyhemoglobin (dHbO2) is paramagnetic and oxyhemoglobin (HbO2) is non-magnetic, the change of concentration of deoxyhemoglobin and oxyhemoglobin can cause a Bulk Magnetic Susceptibility (BMS) change and the T2* signal response during MR imaging. Here, I applied this technique to assess tumor physiological characteristics. In order to study the BOLD mechanism, I designed a phantom system and built it for in-vitro study. Since inhalation of oxygen could cause variation in the blood flow and oxygenation, and BOLD MRI is sensitive to both these factors, it becomes very important to explore the correlation between the BOLD response and these two factors. Considering the different vascular orientation, the angle between vessel and the static magnetic field (BItem Evaluation of Chronic RalGTPase Activation as a Core Specifier of Oncogenic Transformation(2009-01-08) Cheng, Tzuling; White, MichaelRal (RAS-Like) GTPases, RalA and RalB, were originally identified based on sequence similarity to Ras and are directly activated via the Ras effector family Ral guanine nucleotide exchange factors (RalGEFs). Previous studies have demonstrated that RalA and RalB collaborate to maintain tumorigenicity through regulating both proliferation and survival. Remarkably, RalB is specifically required for survival in Ras-dependent tumor cells rather than normal cells, while RalA is required for anchorage-independent proliferation but dispensable for survival. However, the spectrum of cancer cell lineages dependent upon Ral functions for tumor formation is currently unknown. We examined whether Ral pathway activation is required for proliferation of cancer cells with activated Ras, Raf, or PI3K. Our data indicate that the Ral pathway is aberrantly activated and required for maintaining tumorigenicity of cancers that are driven by oncogenes other than Ras. In order to begin to understand how the Ral pathway may be chronically engaged in diverse oncogenic backgrounds, we further examined the expression of RalGEFs in a variety of cells derived from different tissue origin. Our results showed a divergent and complex distribution of RalGEFs among different cell types. In addition, through examination of historical tumor resequenceing efforts, we found several somatic mutations in RalGEFs, including RalGDS and RGL1. Through biochemical and cell biological studies, we find that the RGL1 mutations identified in human breast cancers are gain-of -function mutations, and found the mutations contribute to tumor cell survival through RalB pathway. Furthermore, we showed that chronic activation of RGL1 is sufficient to transform immortalized human mammary epithelial cells. Together, our data suggest RGL1 is a bona fide oncogene. These studies broaden our knowledge about RalGEF-Ral contributions in tumorigenicity, and provide a potential target for cancer therapeutic interventions.Item Genetic Analysis of hox Transcription Factors and Cofactors in the Regulation of Programmed Cell Death in C Elegans(2009-01-14) Potts, Malia Beth; Cameron, ScottIt has been well established that blocking apoptosis can promote cancer. Throughout the animal kingdom, apoptosis is exquisitely regulated in cell-specific and context-specific ways to ensure proper development and tissue homeostasis. In many cases, transcriptional pathways carry out this regulation by mechanisms that are not completely understood. Studies of programmed cell death in the nematode Caenorhabditis elegans provided an essential foundation for understanding the more complex pathways of apoptosis in mammals. More recent work, including my thesis research, has focused on the mechanisms that decide whether individual cells of C. elegans survive or undergo programmed cell death, and has revealed a striking concordance of transcription factors that regulate cell death and that cause cancer in humans when altered by mutation. These findings suggest that mutations affecting these transcriptional pathways can provide a survival advantage to cancer cells, and thus may represent promising novel therapeutic targets.Item Illness Perceptions of Patients with Late-Stage Cancer and Their Partners(2013-01-17) Croom, Andrea Rose; Wiebe,Deborah, Ph.D., M.P.H.As treatments improve and patients with late-stage cancer live longer, it is important to examine factors associated with their psychological adjustment and illness-related behaviors. The current studies used the Common-sense Model of Self-regulation (Leventhal, Brissette, & Leventhal, 2003) to understand how patients and their partners manage the demands of this understudied illness context. The Common-sense Model proposes that individuals create mental representations about their illness to make sense of and develop strategies to manage the illness. The current studies were the first to examine (a) whether patients’ illness perceptions are associated with advanced illness behaviors (e.g., completing advance directives; NCI, 2005), which are crucial for receiving quality care at the end-of-life, and (b) whether perceptions of both patients and partners are associated with psychological adjustment. A dyadic perspective is important because cancer is not an individual experience, but rather affects significant others in the patient’s life. Female patients with late-stage breast, gynecological, or lung cancer and their spouses or unmarried partners independently completed self-report measures of their illness perceptions, relationship experience, psychological adjustment, and advanced illness behaviors (N= 105 patients and 88 partners). Data were examined at both intrapersonal (individual) and interpersonal (dyadic) levels. The first study demonstrated that patients’ individual perceptions of cancer were better predictors of their quality of life than clinical characteristics of cancer (e.g., stage, illness duration). Advanced illness behaviors were associated with higher quality of life and were predicted by illness perceptions (i.e., illness severity and illness coherence), as well as by clinical and personal characteristics. The second study suggested that patients’ and partners’ psychological adjustment reflected their individual illness perceptions, as well as aspects of their relationship (i.e., relationship quality and social constraints in discussing cancer). There was limited evidence that incongruence in patients’ and partners’ illness perceptions was related to poorer adjustment, potentially because illness perception congruence was high. Findings from these studies demonstrate the importance of designing interventions to improve communication between patients, partners, and health care professionals about late-stage cancer beliefs.Item The Impact of Specialized Family Camps On Quality of Life and Hope in Families Who Are Coping with Pediatric Cancer(2012-08-15) Cook, Ellen Claire; Wetherington, Crista E.BACKGROUND: Over the past several decades, specialized summer camps for children with cancer have been shown to have various positive results in those who attend. Family camps have become increasingly popular over the past few years, but the efficacy of family camps for specialized populations has not been well established through research. In addition, few studies have addressed the benefits of the camp experience over time, especially in regard to its impact on quality of life. The aim of this study was to learn whether or not the family camp experience increases the quality of life of families with a child with cancer, and whether or not these changes are maintained after the camp experience ends. In addition, this study examined the impact of camp on levels of hope, and analyzed how hope and social support contribute to the quality of life of those who attend camp. SUBJECTS: A total of 66 families participated in this study. Participants include parents, cancer patients or survivors, and siblings. Thirty-nine families who attended a specialized weekend camp participated in the study, and a control sample of 27 families who did not attend camp was recruited as well. METHOD: Questionnaire data was collected at three time points: pre-camp, post-camp, and a three-month follow up. Measures included a demographic questionnaire, age appropriate versions of the PedsQLTM 4.0 Generic Core Scales, the PedsQLTM 2.0 PedsQLTM 2.0 Family Impact Module, the Hope Scale (Adult and Child versions), the Young Children’s Hope Scale, and a brief follow-up questionnaire. RESULTS: Quality of life did not significantly increase in the camp group in the overall family unit. However, quality of life was shown to be significantly higher in the camp group than the control group at the beginning and end of camp. Siblings demonstrated a significant increase in quality of life when examined separately from the family unit. No significant changes in hope or differences in hope between groups were observed. DISCUSSION: Though this study did not demonstrate the efficacy of family camp as predicted, it did show that individual family members are impacted by camp in different ways. Camp has been show to benefit siblings in particular, which is indicated by improvement in quality of life, hope, and social support in this population. This study also shows that different results may be found using different measures of the same variables. [Keywords: camp, quality of life, hope, family, cancer]Item Ral G-Proteins and the Exocyst Complex are Mediators of the Cellular Response to Nutrients(2012-07-20) Bodemann, Brian Oliver; White, Michael A.The small G-proteins, RalA and RalB, are important mediators of cellular responses to viral infection and nutrient availability. Prior work has demonstrated that the exocyst complex is an important effector of Ral G-protein signaling. The eight member exocyst contains two Ral effector proteins, Exo84 and Sec5, which contribute to distinct cellular responses. During viral infection, RalB promotes the activation of the innate immunity signaling kinase, TBK1, through direct assembly on a Sec5-containing subcomplex of the exocyst. Macroautophagy is an important cellular process which facilitates cellular adaptation to nutrient deprivation as well as the clearance of intracellular pathogens. The study of macroautophagy in mammalian cells has described induction, vesicle nucleation, and membrane elongation complexes as key signaling intermediates driving autophagosome biogenesis. How these components are recruited to nascent autophagosomes is poorly understood, and although much is known about signaling mechanisms that restrain autophagy, the nature of positive inductive signals that can promote autophagy remain cryptic. I report that RalB is localized to nascent autophagosomes. RalB and its effector Exo84 are required for nutrient starvation-induced autophagocytosis, and RalB activation is sufficient to promote autophagosome formation. Through direct binding to Exo84, RalB induces the assembly of ULK1 and Beclin1-VPS34 complexes on the exocyst, which are required for isolation membrane formation and maturation. Thus, RalB-Exo84 signaling is a primary adaptive response to nutrient limitation that directly engages autophagocytosis through mobilization of the core vesicle nucleation machinery. Conversely, I find that Sec5 associates with mTORC1, a key inhibitor of autophagy. Intriguingly, I find that the Ral–Sec5 activated kinase, TBK1, is necessary for amino acid stimulation of mTORC1 activity. Thus, distinct Ral-dependent subcomplexes of the exocyst mediate the cellular response to nutrient availability. [Keywords: RalB, exocyst, autophagy, signal transduction, nutrient sensing]Item Role for NIP45 in Telomere Recruitment to PML Bodies in ALT Cancer Cells(2013-05-14) Farley, Demetra Dannielle; Cobb, Melanie; Yu, Hongtao; Corey, David; Scaglioni, PierTelomere length maintenance is critical for continued cell proliferation. The SMC5/6 complex, required for double-strand break (DSB) repair in both yeast and humans, has been implicated in the maintenance of telomere length in certain cancer cells. In the absence of active telomerase, SMC5/6 complex-dependent homologous recombination is utilized to maintain telomere length at PML bodies, a mechanism referred to as alternative lengthening of telomeres (ALT). Sumoylation of several telomere-binding proteins is required for the localization of telomeres to PML bodies in G2 phase cells (APBs). We demonstrate that NIP45, a SUMO-like domain (SLD) containing protein, also affects telomere targeting in ALT cells. Loss of endogenous NIP45 protein results in decreased localization of telomeres to PML bodies in a manner independent of the SMC5/6 complex. NIP45 stimulates telomere binding protein sumoylation, as knockdown of the NIP45 protein negatively affects their sumoylation. Importantly, the NIP45 C-terminal SUMO-like domain (SLD2) is sufficient to rescue both APB formation and telomere-binding-protein sumoylation. NIP45 localizes to PML bodies, but not telomeres, in log phase cells, yet interacts efficiently with TIN2, a sumoylatable telomere binding protein. Additionally, a fragment of NIP45 containing the functional SLD2 domain is sufficient to maintain TIN2 binding. We predict, then, that NIP45 might act to recruit telomeres to the PML bodies via its interaction with TIN2, ultimately allowing for SMC5/6 complex-dependent telomere maintenance in G2 phase cells. In keeping with this hypothesis, loss of endogenous TIN2 protein also negatively affects localization of telomeres to PML bodies, even in the presence of NIP45, supporting a requirement for the TIN2-NIP45 interaction in telomere localization to PML bodies. Through this work, we have defined a role for the NIP45 protein in ALT cancer cell telomere length maintenance, further detailing the mechanism by which telomerase-negative cancer subtypes achieve unlimited replicative potential.Item Targeting Aminophospholipids Exposed On Tumor Endothelium for Tumor Imaging(2012-07-20) Stafford, Jason Hugh; Thorpe, Philip E.Advances in noninvasive imaging of human cancer are crucial to improving diagnosis and therapeutic planning. My project was aimed at developing novel imaging agents that target the aminophospholipidsphosphatidylserine (PS) and phosphatidylethanolamine (PE). PS and PE arenormally intracellular, but become exposed on the surface of tumor endothelial cells (EC). Anti-tumor therapies promote exposure of PS and PE on tumor EC and the tumor cells as well. Therefore, I tested the hypothesis that 1N11, a PS-binding antibody, and duramycin, a PE-binding peptide, could function as tumor imaging agents. I labeled the F(ab’)2 fragment of 1N11 with the near-infrared fluophore 800CW for optical imaging and the positron emitting isotope iodine-124 (124I) for PET imaging. 800CW-1N11 F(ab’)2 clearly imaged subcutaneous and orthotopic U87 gliomas growing in mice with optimal tumor contrast obtained at 24 h post-injection (p.i.). Uptake of 800CW-1N11 F(ab’)2 was approximately 2-fold higher in irradiated U87 tumors. 124I-1N11 F(ab’)2 clearly imaged subcutaneous and orthotopic PC3 prostate carcinomas growing in mice with optimal tumor contrast obtained at 48 hr p.i. Importantly, 800CW- and 124I-1N11 F(ab’)2 exhibited low uptake in non-target organs (i.e. liver and kidneys). Unlike PS, PE had not been established as a specific marker of tumor vasculature in the literature. To demonstrate PE was such a marker, I biotinylated duramycin, characterized its binding properties, and used it to determine the distribution of PE on EC in vitro and in vivo. Exposure of cultured EC to hypoxia, acidity, reactive oxygen species, or irradiation resulted in the formation of membrane blebs that were intensely PE-positive. When biotinylated duramycin was intravenously injected into tumor-bearing mice it preferentially localized to the luminal surface of the vascular endothelium in multiple tumor models. PE-positive vessels were observed in and around hypoxic regions of the tumor. With the exception of intertubular vessels of the kidney, normal vessels remained unstained. I also conjugated duramycin to 800CW and used it for optical imaging of RM-9 and TRAMP prostate carcinomas. These results demonstrate that both 1N11 and duramycin can be used to image a variety of tumors and warrant further study as imaging agents. [Keywords" cancer, imaging, phospholipids, antibodies, peptides, optical, PET, phosphatidylserine, phosphatidylethanolamine, vasculature]