Biomarkers in preclinical cancer imaging

In view of the trend towards personalized treatment strategies for (cancer) patients, there is an increasing need to noninvasively determine individual patient characteristics. Such information enables physicians to administer to patients accurate therapy with appropriate timing. For the noninvasive visualization of disease-related features, imaging biomarkers are expected to play a crucial role. Next to the chemical development of imaging probes, this requires preclinical studies in animal tumour models. These studies provide proof-of-concept of imaging biomarkers and help determine the pharmacokinetics and target specificity of relevant imaging probes, features that provide the fundamentals for translation to the clinic. In this review we describe biological processes derived from the “hallmarks of cancer” that may serve as imaging biomarkers for diagnostic, prognostic and treatment response monitoring that are currently being studied in the preclinical setting. A number of these biomarkers are also being used for the initial preclinical assessment of new intervention strategies. Uniquely, noninvasive imaging approaches allow longitudinal assessment of changes in biological processes, providing information on the safety, pharmacokinetic profiles and target specificity of new drugs, and on the antitumour effectiveness of therapeutic interventions. Preclinical biomarker imaging can help guide translation to optimize clinical biomarker imaging and personalize (combination) therapies

Inter-comparison of quantitative imaging of lutetium-177 (177Lu) in European hospitals

Background: This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. Results: The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. Conclusions: A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study

Abstract: Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). Methods: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). Results: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). Conclusion: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT

Perspectives on Small Animal Radionuclide Imaging; Considerations and Advances in Atherosclerosis

This review addresses nuclear SPECT and PET imaging in small animals in relation to the atherosclerotic disease process, one of our research topics of interest. Imaging of atherosclerosis in small animal models is challenging, as it operates at the limits of current imaging possibilities regarding sensitivity, and spatial resolution. Several topics are discussed, including technical considerations that apply to image acquisition, reconstruction, and analysis. Moreover, molecules developed for or applied in these small animal nuclear imaging studies are listed, including target-directed molecules, useful for imaging organs or tissues that have elevated expression of the target compared to other tissues, and molecules that serve as substrates for metabolic processes. Differences between animal models and human pathophysiology that should be taken into account during translation from animal to patient as well as differences in tracer behavior in animal vs. man are also described. Finally, we give a future outlook on small animal radionuclide imaging in atherosclerosis, followed by recommendations. The challenges and solutions described might be applicable to other research fields of health and disease as well

Highlights lecture EANM 2015: the search for nuclear medicine’s superheroes

The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1)

Rethinking City-regionalism as the Production of New Non-State Spatial Strategies: The Case of Peel Holdings Atlantic Gateway Strategy

This article was published in the journal, Urban Studies [© Sage]. The publisher's website is at: http://usj.sagepub.com/content/early/2013/08/19/0042098013493481City-regions are widely recognised as key to economic and social revitalization. Hardly surprising then is how policy elites have sought to position their own city-regions strategically within international circuits of capital accumulation. Typically this geopolitics of city-regionalism has been seen to represent a new governmentalised remapping of state space conforming to the prevailing orthodoxy of neoliberal state spatial restructuring. Through a case study of the Atlantic Gateway Strategy, this paper provides a lens on to an alternative vision for city-region development. The brainchild of a private investment group, Peel Holdings, the Atlantic Gateway is important because it points toward the production of new non-state spatial strategies. Examining Peel’s motives for invoking the city-region concept, the paper goes on to explore the tensions which currently surround the strategy to further identify the potential and scope for non-state spatial strategies. Connecting this to emerging debates around the key role of asset ownership and the privatisation of local democracy and the democratic state, the paper concludes by suggesting the key question arising is can and will the state maintain its degree of governmental control over capital investment in major urban regions in an era where persistent under-provision of investment in urban economic infrastructure behoves institutions of the state to become ever more reliant on private investment groups to deliver the deliver the jobs, growth and regeneration of the future

Biomarkers in preclinical cancer imaging

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Perspectives on Small Animal Radionuclide Imaging; Considerations and Advances in Atherosclerosis

This review addresses nuclear SPECT and PET imaging in small animals in relation to the atherosclerotic disease process, one of our research topics of interest. Imaging of atherosclerosis in small animal models is challenging, as it operates at the limits of current imaging possibilities regarding sensitivity,