Parametric imaging of ¹⁸F-fluoro-3-deoxy-3-L-fluorothymidine PET data to investigate tumour heterogeneity.

Purpose: [(18)F]Fluoro-3'-deoxy-3'-L-fluorothymidine ([(18)F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [(18)F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [(18)F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [(18)F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response.

Frequency and significance of physiological versus pathological uptake of 68Ga-DOTATATE in the pancreas: validation with morphological imaging.

Aim: The objective of this study was to assess the relevance of physiological (68)Ga-DOTATATE PET/CT findings in the pancreas guided by morphological imaging (MI) in comparison with pathological tumour uptake in patients with neuroendocrine tumours (NETs).

Methods: A total of 138 patients with pancreatic NET (pNET; n=38) or non-pNET (n=100) underwent (68)Ga-DOTATATE PET/CT. Pancreatic regions with intensity higher than background were localized with anatomical reference support [head/uncinate process (HUP); body/tail (BT)] and classified as tumour, suspicious or physiological.

Preclinical assessment of carboplatin treatment efficacy in lung cancer by 18F-ICMT-11-positron emission tomography.

Tumour response to therapy is assessed primarily in the clinic by monitoring reductions in tumour size. However, this approach lacks sensitivity since in many cases several weeks may elapse before there is evidence of tumour shrinkage. There is therefore a need to develop non-invasive imaging techniques for monitoring tumour treatment response in the clinic.

Elderly demand for family-based care and support: evidence from a social intervention strategy.

This paper examines the influence of the national health insurance scheme on elderly demand for family-based care and support. It contributes to the growing concern on the rapid increase in the elderly population globally using micro-level social theory to examine the influence the health insurance has on elderly demand for family support. A qualitative case study approach is applied to construct a comprehensive and thick description of how the national health insurance scheme influences the elderly in their demand for family support.

RGD-targeted MnO nanoparticles as T contrast agents for cancer imaging - the effect of PEG length in vivo.

As magnetic resonance imaging (MRI) contrast agents, T Gd chelates are generally the preferred option for radiologists over T iron oxide nanoparticles. The main reason for the popularity of T agents is the easier interpretation of T-weighted MR images. However, the chemical versatility of nanoparticulate platforms makes them ideal candidates for the next generation of targeted MRI contrast agents.

PET imaging with multimodal upconversion nanoparticles.

A series of new upconversion nanoparticles have been functionalised with tumour-targeting molecules and metal chelates, prepared following standard peptidic and thiol chemistry. The targeting strategy has been delivered via the αvβ3 integrin, which is a heterodimeric cell surface receptor that is up-regulated in a variety of cancers, such as melanoma and breast cancer. The well-known DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) motif allows coordination to the radionuclide (68)Ga.

Positron emission tomography imaging with 18F-labeled ZHER2:2891 affibody for detection of HER2 expression and pharmacodynamic response to HER2-modulating therapies.

Purpose: Expression of HER2 has profound implications on treatment strategies in various types of cancer. We investigated the specificity of radiolabeled HER2-targeting ZHER2:2891 Affibody, [(18)F]GE-226, for positron emission tomography (PET) imaging.

Experimental Design: Intrinsic cellular [(18)F]GE-226 uptake and tumor-specific tracer binding were assessed in cells and xenografts with and without drug treatment.

Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers.

Unlabelled: (11)C-choline and (18)F-fluoromethylcholine ((18)F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, (18)F-fluoromethyl-[1,2-(2)H4]choline ((18)F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-D4-FCH in 8 healthy human volunteers.

Preclinical evaluation of a CXCR4-specific (68)Ga-labelled TN14003 derivative for cancer PET imaging.

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 (68)Ga, (64)Cu and (111)In as well as (18)F (Al(18)F).

Radiolabeled RGD tracer kinetics annotates differential αvβ 3 integrin expression linked to cell intrinsic and vessel expression.

Purpose: The purpose of this paper is to study the association between RGD binding kinetics and αvβ3 integrin receptor density in the complex tumor milieu.

Procedures: We assessed αvβ3 in vitro and by (68)Ga-DOTA-[c(RGDfK)]2 positron emission tomography (PET) in tumors with varying αvβ3.

Results: Intrinsic αvβ3 expression decreased in the order of M21 >>> MDA-MB-231 > M21L in cells.

Synthesis of a new fluorine-18 glycosylated 'click' cyanoquinoline for the imaging of epidermal growth factor receptor.

This study reports the radiosynthesis of a new fluorine-18 glycosylated 'click' cyanoquinoline [(18) F]5 for positron emission tomography imaging of epidermal growth factor receptor (EGFR). The tracer was obtained in 47.7 ± 7.

Bioorthogonal chemistry for (68) Ga radiolabelling of DOTA-containing compounds.

Copper-catalysed 'click' chemistry is a highly utilised technique for radiolabelling small molecules and peptides for imaging applications. The usefulness of these reactions falls short, however, when metal catalysis is not a practically viable route; such as when using metal chelates as radioligands. Here, we describe a method for carrying out 'click-type' radiochemistry in the presence of DOTA chelates, by combining (68) Ga radiolabelling techniques with well-established bioorthogonal reactions, which do not rely upon metal catalysis.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.

Introduction: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.

Methods: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment.

Exploring the potential of [11C]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer.

Objectives: The aim of the study was to assess the effects of neoadjuvant androgen deprivation (NAD) and radical prostate radiotherapy with concurrent androgen deprivation (RT-CAD) on prostatic [C]choline kinetics and thus develop methodology for the use of [C]choline-PET/computed tomography (CT) as an early imaging biomarker.

Materials And Methods: Ten patients with histologically confirmed prostate cancer underwent three sequential dynamic [C]choline-PET/CT pelvic scans: at baseline, after NAD and 4 months after RT-CAD. [C]Choline uptake was quantified using the average and maximum standardized uptake values at 60 min (SUV60,ave and SUV60,max), the tumour-to-muscle ratios (TMR60,max) and net irreversible retention of [C]choline at steady state (Kimod-pat).

Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance.

Background: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.

Methods: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.

Maternal health-seeking behavior: the role of financing and organization of health services in Ghana.

This paper examines how organization and financing of maternal health services influence health-seeking behavior in Bosomtwe district, Ghana. It contributes in furthering the discussions on maternal health-seeking behavior and health outcomes from a health system perspective in sub-Saharan Africa. From a health system standpoint, the paper first presents the resources, organization and financing of maternal health service in Ghana, and later uses case study examples to explain how Ghana's health system has shaped maternal health-seeking behavior of women in the district.

18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry.

Unlabelled: Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, (18)F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), has been developed for use in PET studies.

Visualising androgen receptor activity in male and female mice.

Androgens, required for normal development and fertility of males and females, have vital roles in the reproductive tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a ligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic "ARE-Luc" mouse, expressing a luciferase reporter gene under the control of activated endogenous AR.

Bioorthogonal chemistry for pre-targeted molecular imaging--progress and prospects.

The aim of this perspective is to critically review the three most prominent bioorthogonal reactions that are used presently, on both a purely chemical level and in the context of biological systems. This includes the uses both for synthesis of therapeutic molecules, modification of large biomolecules or antibodies, and in particular, the exciting use in the field of 'pre-targeting', for both possible treatment and imaging technologies. We will compare the validity of each reaction when compared to others, and their usefulness in biological systems, as each methodology has clear advantages over the others in differing environments.

Design, synthesis and in vitro characterization of fluorescent and paramagnetic CXCR4-targeted imaging agents.

The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core, encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to the CXCR4 receptor.

Heterogeneity in lung (18)FDG uptake in pulmonary arterial hypertension: potential of dynamic (18)FDG positron emission tomography with kinetic analysis as a bridging biomarker for pulmonary vascular remodeling targeted treatments.

Background: Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models.

Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer.

Magnetic nanoparticles represent one of the most advanced developments in the application of nanotechnology to human health. To date, their clinical application has been restricted to the diagnosis of hepatic lesions and lymph node metastasis but functionalization of these materials with biomolecules as targeting motifs, and the inclusion of therapeutic drugs in their composition, is certain to make a substantial impact within biomedicine. One of the diseases that could benefit from these advances is cancer, as early diagnosis and effective treatment are crucial for a patient's survival and quality of life.

Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging.

Purpose: Induction of apoptosis in tumors is considered a desired goal of anticancer therapy. We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [(18)F]ICMT-11 and positron emission tomography (PET).

Experimental Design: The effects of a single dose of the alkylating agent cyclophosphamide (CPA or 4-hydroperoxycyclophosphamide), or the mechanism-based small molecule SMAC mimetic birinapant on caspase-3 activation was assessed in vitro and by [(18)F]ICMT-11-PET in mice bearing 38C13 B-cell lymphoma, HCT116 colon carcinoma, or MDA-MB-231 breast adenocarcinoma tumors.

A phantom for diffusion-weighted MRI (DW-MRI).

Purpose: To develop tissue-equivalent diffusivity materials and build a spherical diffusion phantom which mimics the conditions typically found in biological tissues. Also, to assess the reproducibility of ADC measurements from a whole-body diffusion protocol.

Materials And Methods: Nickel-doped agarose/sucrose gels were manufactured and used to build a spherical diffusion phantom with tissue-equivalent relaxation and diffusion compartments.