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Witney T.H.,Comprehensive Cancer Imaging Center | Carroll L.,Comprehensive Cancer Imaging Center | Alam I.S.,Comprehensive Cancer Imaging Center | Chandrashekran A.,Comprehensive Cancer Imaging Center | And 6 more authors.
Cancer Research | Year: 2014

The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG- PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that 18F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3] triazole-4-yl)glucosamine (18F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating 18F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited 18F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, 18F-NFTG, but not 18F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence. © 2013 American Association for Cancer Research.

Merchant S.,Comprehensive Cancer Imaging Center | Witney T.H.,Comprehensive Cancer Imaging Center | Aboagye E.O.,Comprehensive Cancer Imaging Center
Clinical and Translational Imaging | Year: 2014

Imaging of biological and molecular processes has provided the platform for evaluating the hallmarks of cancer, such as metabolism, proliferation, tissue invasion, angiogenesis, apoptosis and hypoxia, and in turn for assessing the efficacy of treatments including novel targeted therapies. Cross-sectional imaging methods can measure response to chemotherapy and radiotherapy by measuring changes in tumour volume. Imaging modalities such as positron emission tomography and functional magnetic resonance imaging can non-invasively detect early molecular changes in response to therapy, provide guidance for therapy optimisation, and predict response to treatments and clinical outcome. In an era of escalating drug trial costs, with high attrition rates of early-phase studies, the development of an imaging biomarker can contribute to optimisation of proof of concept and patient stratification. In this review, we examine the current molecular imaging modalities used to assess pharmacodynamics and therapy response and highlight some novel emerging imaging strategies. © 2014 Italian Association of Nuclear Medicine and Molecular Imaging.

Pisaneschi F.,Comprehensive Cancer Imaging Center | Witney T.H.,Comprehensive Cancer Imaging Center | Iddon L.,Comprehensive Cancer Imaging Center | Aboagye E.O.,Comprehensive Cancer Imaging Center
MedChemComm | Year: 2013

[18F]Fluoro-pivalic acid ([18F]FPIA), an analogue of [18F]fluoroacetate bearing a dimethyl moiety on C-2, has been radiosynthesised and evaluated in vivo. [18F]FPIA has high tumour uptake and, unlike [18F]fluoroacetate, does not defluorinate. © 2013 The Royal Society of Chemistry.

George G.P.C.,Comprehensive Cancer Imaging Center | George G.P.C.,Imperial College London | Stevens E.,Comprehensive Cancer Imaging Center | Aberg O.,Comprehensive Cancer Imaging Center | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2014

Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. In our pursuit of a CXCR4-specific radiotracer, we designed and synthesised a novel derivative of the CXCR4 peptidic antagonist TN14003, CCIC16, which is amenable to radiolabelling by chelation with a range of PET and SPECT radiometals, such as 68Ga, 64Cu and 111In as well as 18F (Al18F). Potent in vitro binding affinity and inhibition of signalling-dependent cell migration by unlabelled CCIC16 were confirmed by a threefold uptake in CXCR4-over-expressing cells compared to their isogenic counterparts. Furthermore, in vivo experiments demonstrated the favourable pharmacokinetic properties of the 68Ga-labelled tracer 68Ga-CCIC16, along with its CXCR4-specific accumulation in tissues with desirable contrast (tumour-to-muscle ratio: 9.5). The specificity of our tracer was confirmed by blocking experiments. Taking into account the attractive intrinsic PET imaging properties of 68Ga, the comprehensive preclinical evaluation presented here suggests that 68Ga-CCIC16 is a promising PET tracer for the specific imaging of CXCR4-expressing tumours. © 2013 Elsevier Ltd. All rights reserved.

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