Effect of Fiber Loading on Mechanical and Flame-Retardant Properties of Poplar-Fiber-Reinforced Gypsum Composites.

Gypsum-based composites were prepared via a slurry casting process using construction gypsum as the binding material and poplar fibers as reinforcing material. The effects of different fiber content and curing time on the mechanical properties, water resistance, and flame retardancy of these composites were investigated, and the influence mechanism was characterized by infrared spectroscopy, scanning electron microscopy, and X-ray diffractometry. The results showed that the best composite mechanical strength was achieved with 10% poplar fiber- content, and the absolute dry flexural and compressive strengths reached 3.59 and 8.06 MPa, respectively. Compared with pure gypsum, the flexural strength and compressive strength increased by 10% and 19%, respectively. The inclusion of fibers somewhat prevented the migration of free water within the composites and enhanced their water resistance. At 10% fiber content, the composite's 24 h water absorption rate was 34.3%, 8% lower than that of pure gypsum, with a softening coefficient of 0.55. However, fiber content increases the porosity of gypsum-based composites. When heated, this increased porosity accelerates' heat conduction within the matrix, raising the peak and total exothermic rates, thereby weakening the composites' inherently flame-retardant properties. Poplar-fiber-reinforced gypsum-based composites offered superior performance in commercial applications, compared to pure gypsum board, providing a sustainable and green alternative for ceilings, partitions, and other applications, while broadening the prospects for gypsum-based composites in the engineering field.

Imaging the effect of ketamine on synaptic density (SV2A) in the living brain.

The discovery of ketamine as a rapid and robust antidepressant marks the beginning of a new era in the treatment of psychiatric disorders. Ketamine is thought to produce rapid and sustained antidepressant effects through restoration of lost synaptic connections. We investigated this hypothesis in humans for the first time using positron emission tomography (PET) and [11C]UCB-J-a radioligand that binds to the synaptic vesicle protein 2A (SV2A) and provides an index of axon terminal density. Overall, we did not find evidence of a measurable effect on SV2A density 24 h after a single administration of ketamine in non-human primates, healthy controls (HCs), or individuals with major depressive disorder (MDD) and/or posttraumatic stress disorder (PTSD), despite a robust reduction in symptoms. A post-hoc, exploratory analysis suggests that patients with lower SV2A density at baseline may exhibit increased SV2A density 24 h after ketamine. This increase in SV2A was associated with a reduction in depression severity, as well as an increase in dissociative symptoms. These initial findings suggest that a restoration of synaptic connections in patients with lower SV2A at baseline may underlie ketamine's therapeutic effects, however, this needs replication in a larger sample. Further work is needed to build on these initial findings and further establish the nuanced pre- and post-synaptic mechanisms underpinning ketamine's therapeutic effects.

Unsupervised-learning-based calibration method in microscopic fringe projection profilometry.

Microscopic fringe projection profilometry (MFPP) technology is widely used in 3D measurement. The measurement precision performed by the MFPP system is closely related to the calibration accuracy. However, owing to the shallow depth of field, calibration in MFPP is frequently influenced by low-quality target images, which would generate inaccurate features and calibration parameter estimates. To alleviate the problem, this paper proposes an unsupervised-learning-based calibration robust to defocus and noise, which could effectively enhance the image quality and increase calibration accuracy. In this method, first, an unsupervised image deblurring network (UIDNet) is developed to recover a sharp target image from the deteriorated one. Free from capturing strictly paired images by a specific vision system or generating the dataset by simulation, the unsupervised deep learning framework can learn more accurate features from the multi-quality target dataset of convenient image acquisition. Second, multi-perceptual loss and Fourier frequency loss are introduced into the UIDNet to improve the training performance. Third, a robust calibration compensation strategy based on 2D discrete Fourier transform is also developed to evaluate the image quality and improve the detection accuracy of the reference feature centers for fine calibration. The relevant experiments demonstrate that the proposed calibration method can achieve superior performance in terms of calibration accuracy and measurement precision.

Imaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET).

PURPOSE: Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue. METHODS: We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [11C]UCB-J and [18F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot. RESULTS: Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures. CONCLUSION: While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain.

Synthesis and in Vitro and in Vivo Evaluation of MMP-12 Selective Optical Probes.

In designing new tracers consisting of a small peptide conjugated to a reporter of comparable size, particular attention needs to be paid to the selection of the reporter group, which can dictate both the in vitro and the in vivo performances of the whole conjugate. In the case of fluorescent tracers, this is particularly true given the large numbers of available dye moieties differing in their structures and properties. Here, we have investigated the in vitro and in vivo properties of a novel series of MMP-12 selective probes composed of cyanine dyes varying in their structure, net charge, and hydrophilic character, tethered through a linker to a potent and specific MMP-12 phosphinic pseudopeptide inhibitor. The impact of linker length has been also explored. The crystallographic structure of one tracer in complex with MMP-12 has been obtained, providing the first crystal structure of a Cy5.5-derived probe and confirming that the binding of the targeting moiety is unaffected. MMP-12 remains the tracers' privileged target, as attested by their affinity selectivity profile evaluated in solution toward a panel of 12 metalloproteases. In vivo assessment of four selected probes has highlighted not only the impact of the dye structure but also that of the linker length on the probes' blood clearance rates and their biodistributions. These experiments have also provided valuable data on the stability of the dye moieties in vivo. This has permitted the identification of one probe, which combines favorable binding to MMP-12 in solution and on cells with optimized in vivo performance including blood clearance rate suitable for short-time imaging. Through this series of tracers, we have identified various critical factors modulating the tracers' in vivo behavior, which is both useful for the development and optimization of MMP-12 selective radiolabeled tracers and informative for the design of fluorescent probes in general.

Positron Emission Tomography Imaging of Vessel Wall Matrix Metalloproteinase Activity in Abdominal Aortic Aneurysm.

BACKGROUND: Matrix metalloproteinases (MMPs) play a key role in the pathogenesis of abdominal aortic aneurysm (AAA). Imaging aortic MMP activity, especially using positron emission tomography to access high sensitivity, quantitative data, could potentially improve AAA risk stratification. Here, we describe the design, synthesis, characterization, and evaluation in murine AAA and human aortic tissue of a first-in-class MMP-targeted positron emission tomography radioligand, 64Cu-RYM2. METHODS: The broad spectrum MMP inhibitor, RYM2 was synthetized, and its potency as an MMP inhibitor was evaluated by a competitive inhibition assay. Toxicology studies were performed. Tracer biodistribution was evaluated in a murine model of AAA induced by angiotensin II infusion in Apolipoprotein E-deficient mice. 64Cu-RYM2 binding to normal and aneurysmal human aortic tissues was assessed by autoradiography. RESULTS: RYM2 functioned as an MMP inhibitor with nanomolar affinities. Toxicology studies showed no adverse reaction in mice. Upon radiolabeling with Cu-64, the resulting tracer was stable in murine and human blood in vitro. Biodistribution and metabolite analysis in mice showed rapid renal clearance and acceptable in vivo stability. In vivo positron emission tomography/computed tomography in a murine model of AAA showed a specific aortic signal, which correlated with ex vivo measured MMP activity and Cd68 gene expression. 64Cu-RYM2 specifically bound to normal and aneurysmal human aortic tissues in correlation with MMP activity. CONCLUSIONS: 64Cu-RYM2 is a first-in-class MMP-targeted positron emission tomography tracer with favorable stability, biodistribution, performance in preclinical AAA, and importantly, specific binding to human tissues. These data set the stage for 64Cu-RYM2-based translational imaging studies of vessel wall MMP activity, and indirectly, inflammation, in AAA.

Near-infrared fluorescent divalent RGD ligand for integrin αvß3-targeted optical imaging.

A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin α(v)ß(3)-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable improvements in integrin α(v)ß(3) binding affinity and tumor uptake in nude mice of A549. The results suggest that cypate-linked divalent ligands can serve as an important molecular platform for exploring receptor-targeted optical imaging and treatment of various diseases.

Effects of Reed Biochar Mass Fraction on the Properties of Polypropylene/Reed Char Composites.

Reed charcoal/polypropylene (RC/PP) composites were prepared by melt-blending and molding processes. The effects of RC addition (by mass fraction) on its mechanical properties were investigated and the mechanism characterized. The results showed that RC and PP were physically bonded and formed a mechanical interlocking matrix. The water absorption rate of these composites was <1% at 168 h. As the RC mass fraction increased, the tensile modulus, crystallinity, and energy storage modulus of the composites increased and then decreased, with the tensile modulus reaching a maximum of 679.4 MPa. The thermal decomposition rate peak and starting melt temperature increased by 14.8 and 2.5 °C, respectively, compared to pure PP, and the energy storage modulus reached a maximum of 3752.8 MPa at 40 wt% RC. The addition of RC in appropriate amounts improved the rigidity and thermal stability of these composites.

Effect of different amounts of bamboo charcoal on properties of biodegradable bamboo charcoal/polylactic acid composites.

Biodegradable composites were prepared from polylactic acid (PLA) and bamboo charcoal (BC) by melt blending and hot pressing. The effects of BC addition on the mechanical properties, water absorption, DMA, TGA, DSC, and CONE of BC/PLA composites were investigated. The microscopic morphology of the composites was analyzed by SEM. The results showed that for BC addition of 40 wt%, the mechanical strength, thermal properties, and flame retardant properties of the composites were improved compared with those of PLA, with a 2.24 % increase in flexural strength and a 1535 % increase (500 °C) in TG mass retention rate. The crystallinity increased by 129.66 %, the peak loss factor decreased by 31.15 %, the time required for combustion was delayed by 168 s, the peak heat release rate decreased by 29.40 %, the carbon residue rate detected by cone calorimetry increased by 48.50 %, and the peak mass loss rate decreased by 48.82 %. The addition of BC enhanced the crystallization capacity of PLA, and improved the thermal properties and flame retardant properties of the prepared composites. The results showed that materials prepared with a BC content of 40 wt% exhibited the best overall performance.

Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging.

We synthesized disulfide-based cyclic RGD pentapeptides bearing a near-infrared fluorescent dye (cypate), represented by cypate-c(CRGDC) (1) for integrin-targeted optical imaging. These compounds were compared with the traditional lactam-based cyclic RGD counterpart, cypate-c(RGDfK) (2). Molecular modeling suggests that the binding affinity of 2 to integrin α(v)ß(3) is an order of magnitude higher than that of 1. This was confirmed experimentally, which further showed that substitution of Gly with Pro, Val and Tyr in 1 remarkably hampered the α(v)ß(3) binding. Interestingly, cell microscopy with A549 cells showed that 1 exhibited higher cellular staining than 2. These results indicate that factors other than receptor binding affinity to α(v)ß(3) dimeric proteins mediate cellular uptake. Consequently, 1 and its analogs may serve as valuable molecular probes for investigating the selectivity and specificity of integrin targeting by optical imaging.

Synthesis and evaluation of new iRGD peptide analogs for tumor optical imaging.

Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conjugates, that is, Ac-Cys(IRDye®800CW)-iRGD (1), and its dual labeling analog DOTA-Cys(IRDye®800CW)-iRGD (2) were synthesized via the specific mercapto-maleimide reaction for tumor imaging. Both 1 and 2 showed significant tumor localization in optical imaging of MDA-MB-435 tumor-bearing mice. The potential of such iRGD compounds in tumor-targeted imaging and drug delivery deserves further exploration.

Augmented Reality in Ophthalmology: Applications and Challenges.

Augmented reality (AR) has been developed rapidly and implemented in many fields such as medicine, maintenance, and cultural heritage. Unlike other specialties, ophthalmology connects closely with AR since most AR systems are based on vision systems. Here we summarize the applications and challenges of AR in ophthalmology and provide insights for further research. Firstly, we illustrate the structure of the standard AR system and present essential hardware. Secondly, we systematically introduce applications of AR in ophthalmology, including therapy, education, and clinical assistance. To conclude, there is still a large room for development, which needs researchers to pay more effort. Applications in diagnosis and protection might be worth exploring. Although the obstacles of hardware restrict the development of AR in ophthalmology at present, the AR will realize its potential and play an important role in ophthalmology in the future with the rapidly developing technology and more in-depth research.

Assessment of transient dopamine responses to smoked cannabis.

BACKGROUND: Dopaminergic mechanisms that may underlie cannabis' reinforcing effects are not well elucidated in humans. This positron emission tomography (PET) imaging study used the dopamine D2/3 receptor antagonist [11C]raclopride and kinetic modelling testing for transient changes in radiotracer uptake to assess the striatal dopamine response to smoked cannabis in a preliminary sample. METHODS: PET emission data were acquired from regular cannabis users (n = 14; 7 M/7 F; 19-32 years old) over 90 min immediately after [11C]raclopride administration (584 ± 95 MBq) as bolus followed by constant infusion (Kbol = 105 min). Participants smoked a cannabis cigarette, using a paced puff protocol, 35 min after scan start. Plasma concentrations of Δ9-THC and metabolites and ratings of subjective "high" were collected during imaging. Striatal dopamine responses were assessed voxelwise with a kinetic model testing for transient reductions in [11C]raclopride binding, linear-parametric neurotransmitter PET (lp-ntPET) (cerebellum as a reference region). RESULTS: Cannabis smoking increased plasma Δ9-THC levels (peak: 0-10 min) and subjective high (peak: 0-30 min). Significant clusters (>16 voxels) modeled by transient reductions in [11C]raclopride binding were identified for all 12 analyzed scans. In total, 26 clusters of significant responses to cannabis were detected, of which 16 were located in the ventral striatum, including at least one ventral striatum cluster in 11 of the 12 analyzed scans. CONCLUSIONS: These preliminary data support the sensitivity of [11C]raclopride PET with analysis of transient changes in radiotracer uptake to detect cannabis smoking-induced dopamine responses. This approach shows future promise to further elucidate roles of mesolimbic dopaminergic signaling in chronic cannabis use. ClinicalTrials.gov Identifier: NCT02817698.

Association of Aß deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB-J.

BACKGROUND: Attempts to associate amyloid-ß (Aß) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aß plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aß reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aß deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aß deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aß accumulation) compared to those with dementia (a stage of relative Aß plateau). METHODS: We measured SV2A binding ([11C]UCB-J) and Aß deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aß deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aß deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. RESULTS: We observed a significant inverse association between global Aß deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aß deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aß deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aß deposition and SV2A binding in the hippocampus. CONCLUSIONS: Our findings lend support to a model in which fibrillar Aß is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aß may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aß deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.

Hydroxamate-Based Selective Macrophage Elastase (MMP-12) Inhibitors and Radiotracers for Molecular Imaging.

Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CGA, CGA-1, and AGA) and the methodology to obtain MMP-12 selectivity from hydroxamate-based panMMP inhibitors. Also, we report two 99mTc-radiotracers, 99mTc-AGA-1 and 99mTc-AGA-2, derived from AGA. 99mTc-AGA-2 displayed faster blood clearance in mice and better radiochemical stability compared to 99mTc-AGA-1. Based on this, 99mTc-AGA-2 was chosen as the lead tracer and tested in murine AAA. 99mTc-AGA-2 uptake detected by autoradiography was significantly higher in AAA compared to normal aortic regions. Specific binding of the tracer to MMP-12 was demonstrated through ex vivo competition. Accordingly, this study introduces a novel family of selective MMP-12 inhibitors and tracers, paving the way for further development of these agents as therapeutic and imaging agents.

In vivo fluorescence lifetime tomography.

Local molecular and physiological processes can be imaged in vivo through perturbations in the fluorescence lifetime (FLT) of optical imaging agents. In addition to providing functional information, FLT methods can quantify specific molecular events and multiplex diagnostic and prognostic information. We have developed a fluorescence lifetime diffuse optical tomography (DOT) system for in vivo preclinical imaging. Data is captured using a time-resolved intensified charge coupled device (ICCD) system to measure fluorescence excitation and emission in the time domain. Data is then converted to the frequency domain, and we simultaneously reconstruct images of yield and lifetime using an extension to the normalized Born approach. By using differential phase measurements, we demonstrate DOT imaging of short lifetimes (from 350 ps) with high precision (+/-5 ps). Furthermore, this system retains the efficiency, speed, and flexibility of transmission geometry DOT. We demonstrate feasibility of FLT-DOT through a progressive series of experiments. Lifetime range and repeatability are first measured in phantoms. Imaging of subcutaneous implants then verifies the FLT-DOT approach in vivo in the presence of inhomogeneous optical properties. Use in a common research scenario is ultimately demonstrated by imaging accumulation of a targeted near-infrared (NIR) fluorescent-labeled peptide probe (cypate-RGD) in a mouse with a subcutaneous tumor.

Novel Matrix Metalloproteinase 12 Selective Radiotracers for Vascular Molecular Imaging.

Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel 99mTc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their 99gTc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12. Their radiolabeling with 99mTc was shown to be efficient and stable in both buffer and mouse blood. The tracers showed major differences in their biodistribution and blood clearance. On the basis of its in vivo performance, [99mTc]-1 was selected for evaluation in murine AAA, where MMP-12 gene expression is upregulated. Autoradiography of aortae at 2 h postinjection revealed high uptake of [99mTc]-1 in AAA relative to adjacent aorta. Tracer uptake specificity was demonstrated through in vivo competition. This study paves the way for further evaluation of [99mTc]-1 for imaging AAA and other MMP-12-associated diseases.

Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, 99mTc-labeling, and Evaluation.

Matrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing macrocyclic hydroxamate analog, RYM, its hydrazinonicotinamide conjugate, RYM1 and 99mTc-labeled analog 99mTc-RYM1 for molecular imaging. RYM exhibited potent inhibition against a panel of recombinant human (rh) MMPs in vitro. RYM1 was efficiently labeled with 99mTcO4- to give 99mTc-RYM1 in a high radiochemical yield and high radiochemical purity. RYM1 and its decayed labeling product displayed similar inhibition potencies against rhMMP-12. Furthermore, 99mTc-RYM1 exhibited specific binding with lung tissue from lung-specific interleukin-13 transgenic mice, in which MMP activity is increased in conjunction with tissue remodeling and inflammation. The results support further development of such new water-soluble Arginine-containing macrocyclic hydroxamate MMP inhibitors for targeted imaging and therapy.

Modulation of nuclear internalization of Tat peptides by fluorescent dyes and receptor-avid peptides.

The nuclear internalization of biomolecules by Tat peptide provides a mechanism to deliver drugs to cells. However, translocation of molecular imaging probes to the nucleus may induce undesirable mutagenesis. To assess the feasibility of retaining its cell permeating effect without nuclear translocation, Tat-peptide was conjugated with a somatostatin receptor (STR)-avid ligand (Oct) and labeled with fluorescent dyes. The results show that Tat-Oct-5-FAM (fluorescein 5'-carboxylic acid) remained in the cytoplasm of STR-positive AR42J cells. Co-incubation of Tat-Oct-5-FAM with ATP induced nuclear translocation. These data suggest that both dye and Oct-STR endocytosis complex could modulate nuclear internalization of Tat peptides.

Noninvasive imaging of osteoclasts in parathyroid hormone-induced osteolysis using a 64Cu-labeled RGD peptide.

UNLABELLED: Bone diseases are often a result of increased numbers of osteoclasts, or bone-resorbing cells. Bone metastases are a significant cause of morbidity in many types of cancer. An imaging agent targeting osteoclasts, which are upregulated in osteolytic lesions, may facilitate earlier follow-up in patients with osteolytic or mixed bone metastases. Osteoclasts express high levels of alpha(v)beta3 integrin, to which peptides containing the Arg-Gly-Asp (RGD) sequence are known to bind. We proposed that radiolabeled RGD peptides could be used to detect osteoclasts in lytic bone lesions. METHODS: The cross-bridged macrocyclic chelator 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CB-TE2A) was conjugated to c(RGDyK) for radiolabeling with 64Cu (t(1/2), 12.7 h; beta+, 17.4%; E(beta+ max), 656 keV; beta-, 39%; E(beta- max), 573 keV). The in vitro affinity of Cu(II)-CB-TE2A-c(RGDyK) for alpha(v)beta3 and alpha(v)beta5 was evaluated in a heterologous competitive binding assay. Ex vivo uptake was examined in osteoclasts prepared from bone marrow macrophages. As a proof of principle, biodistribution and imaging studies were performed on parathyroid hormone (PTH)-induced osteolysis in the calvarium. RESULTS: Cu-CB-TE2A-c(RGDyK) was shown to have a 30-fold higher affinity for alpha(v)beta3 than for alpha(v)beta5. Osteoclasts were shown to specifically take up (64)Cu-CB-TE2A-c(RGDyK). However, bone marrow macrophages showed only nonspecific uptake. PTH treatment increased calvarial uptake of 64Cu-CB-TE2A-c(RGDyK), compared with uptake in mice receiving a sham treatment. In addition, calvarial uptake correlated linearly with the number of osteoclasts on the bone surface. CONCLUSION: These results suggest that 64Cu-CB-TE2A-c(RGDyK) selectively binds alpha(v)beta3 on osteoclasts and may potentially be used to identify increased numbers of osteoclasts in osteolytic bone diseases such as osteolytic bone metastasis and inflammatory osteolysis.