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Objective: In preclinical studies, high-throughput positron emission tomography (PET) imaging, known as simultaneous multiple animal scanning, can reduce the time spent on animal experiments, the cost of PET tracers, and the risk of synthesis of PET tracers. It is well known that the image quality acquired by high-throughput imaging depends on the PET system. Herein, we investigated the influence of large field of view (FOV) PET scanner on high-throughput imaging. Methods: We investigated the influence of scanning four objects using a small animal PET scanner with a large FOV. We compared the image quality acquired by four objects scanned with the one acquired by one object scanned using phantoms and animals. We assessed the image quality with uniformity, recovery coefficient (RC), and spillover ratio (SOR), which are indicators of image noise, spatial resolution, and quantitative precision, respectively. For the phantom study, we used the NEMA NU 4-2008 image quality phantom and evaluated uniformity, RC, and SOR, and for the animal study, we used Wistar rats and evaluated the spillover in the heart and kidney. Results: In the phantom study, four phantoms had little effect on imaging quality, especially SOR compared with that for one phantom. In the animal study as well, four rats had little effect on spillover from the heart muscle and kidney cortex compared with that for one rat. Conclusions: This study demonstrated that an animal PET scanner with a large FOV was suitable for high-throughput imaging. Thus, the large FOV PET scanner can support drug discovery and bridging research through rapid pharmacological and pathological evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p

Purpose: In this study, a small animal PET insert (SimPET-X, Brightonix Imaging Inc.) for simultaneous PET/MR imaging studies is presented. This insert covers an 11-cm-long axial field-of-view (FOV) and enables imaging of mouse total-bodies and rat heads. Procedures: SimPET-X comprises 16 detector modules to yield a ring diameter of 63 mm and an axial FOV of 110 mm. The detector module supports four detector blocks, each comprising two 4 × 4 SiPM arrays coupled with a 20 × 9 array of LSO crystals (1.2 × 1.2 × 10 mm3). The physical characteristics of SimPET-X were measured in accordance with the NEMA NU4-2008 standard protocol. In addition, we assessed the compatibility of SimPET-X with a small animal-dedicated MRI (M7, Aspect Imaging) and conducted phantom and animal studies. Results: The radial spatial resolutions at the center based on 3D OSEM without and with the warm background were 0.73 mm and 0.99 mm, respectively. The absolute peak sensitivity of the system was 10.44% with an energy window of 100–900 keV and 8.27% with an energy window of 250–750 keV. The peak NECR and scatter fraction for the mouse phantom were 348 kcps at 26.2 MBq and 22.1% with an energy window of 250–750 keV, respectively. The standard deviation of pixel value in the uniform region of an NEMA IQ phantom was 4.57%. The spillover ratios for air- and water-filled chambers were 9.0% and 11.0%, respectively. In the hot-rod phantom image reconstructed using 3D OSEM-PSF, all small rods were resolved owing to the high spatial resolution of the SimPET-X system. There was no notable interference between SimPET-X and M7 MRI. SimPET-X provided high-quality mouse images with superior spatial resolution, sensitivity, and counting rate performance. Conclusion: SimPET-X yielded a remarkably improved sensitivity and NECR compared with SimPETTM. [ABSTRACT FROM AUTHOR]

Background: Expression of translocator protein (TSPO) on the outer mitochondrial membrane of activated microglia is strongly associated with neuroinflammation. The second-generation PET ligand [18F]FEPPA specifically binds TSPO to enable in vivo visualization and quantification of neuroinflammation. We optimized a fully automated radiosynthesis method and evaluated the utility of [18F]FEPPA, the second-generation PET ligand specifically binds TSPO, in a mouse model of systemic LPS challenge to detect TSPO-associated signals of central and peripheral inflammation. In vivo dynamic PET/MR imaging was performed in LPS-induced and control mice after [18F]FEPPA administration. The relationship between the [18F]FEPPA signal and the dose of LPS was assessed. The cytokine levels (i.e., TNF-α, Il-1β, Il-6) in LPS-induced mice were measured by RT-PCR. Standard uptake value (SUV), total volume of distribution (VT) and area under the curve (AUC) were determined based on the metabolite-uncorrected plasma input function. Western blotting and immunostaining were used to measure TSPO expression in the brain. Results: The fully automated [18F]FEPPA radiosynthesis produced an uncorrected radiochemical yield of 30 ± 2% within 80 min, with a radiochemical purity greater than 99% and specific activity of 148.9‒216.8 GBq/µmol. Significant differences were observed in the brain after [18F]FEPPA administration: SUV, VT and AUC were 1.61 ± 0.1, 1.25 ± 0.12 and 1.58 ± 0.09-fold higher in LPS-injected mice than controls. TNF-α, Il-1β and Il-6 mRNA levels were also elevated in the brains of LPS-injected mice. Western blotting revealed TSPO (p < 0.05) and Iba-1 (p < 0.01) were upregulated in the brain after LPS administration. In LPS-injected mice, TSPO immunoactivity colocalized with Iba-1 in the cerebrum and TSPO was significantly overexpressed in the hippocampus and cerebellum. The peripheral organs (heart, lung) of LPS-injected mice had higher [18F]FEPPA signal-to-noise ratios than control mice. Conclusions: Based on the current data on ligand specificity and selectivity in central tissues using 7 T PET/MR imaging, we demonstrate that [18F]FEPPA accumulations significant increased in the specific brain regions of systemic LPS-induced neuroinflammation (5 mg/kg). Future investigations are needed to determine the sensitivity of [18F]FEPPA as a biomarker of neuroinflammation as well as the correlation between the PET signal intensity and the expression levels of TSPO. [ABSTRACT FROM AUTHOR]

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using longchain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid (18F-FTHA) and glucose analog 18F-fluorodeoxyglucose (18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol (18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4X10-8 ), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5X10-6 ) and distribution volume (P = 3X10-8 ), significantly higher 18F-FDG myocardial influx rate constant (P = 3X10-8 ), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH. [ABSTRACT FROM AUTHOR]

Malignant gliomas are the most common primary tumors that arise from glial cells and are characterized by extensive invasiveness and rapid progression. Limitation of the current therapeutic regimen for malignant glioma warrants the development of new therapies strategies. In order to investigate new methods of therapy, establishment of a reliable animal model is essential both in studying the tumor biology and trialing a new therapeutic strategy. Noninvasive monitoring of tumor growth in living animals may be important for new therapeutic strategy development. The development of animal imaging techniques has improved our ability to investigate animal models of malignant gliomas. In this study, both neurological examination and positron emission tomography (PET) with F-FDG were used to monitor tumor growth in a rat glioma model. Visual limb placing, tactile limb placing, and beam walking tests were used to assess neurological deficits. Neurobehavioral alterations were correlated with PET findings and histopathological data. Seven days after surgery, the tumor was clearly visible on PET images. Results of behavioral tests correlated well with imaging data and histopathological findings. PET is feasible to detect experimental rat gliomas in their early stage of development. In contrast, standard neurological assessment is useful for monitoring tumor growth during the course of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Attenuation correction (AC) is important in quantitative positron emission tomography (PET) imaging of medium-sized animals such as the cat. However, additional time for transmission (TX) scanning and tracer uptake is required in PET studies with animal-dedicated PET scanners because post-injection TX scanning is not available in these systems. The aim of this study was to validate a template-guided AC (TGAC) method that does not require TX PET data for AC in cat 2-deoxy-2-[F-(18)fluoro-D-glucose (FDG) brain PET imaging.Methods: PET scans were acquired using a microPET Focus 120 scanner. TX data were obtained using a (68)Ge point source before the injection of FDG. To generate the attention map (mu-map) template for the TGAC, a target image of emission (EM) PET was selected, and spatial normalization parameters of individual EM data onto the target were reapplied to the corresponding mu-maps. The inverse transformations of the mu-map template into the individual spaces were performed, and the transformed template was forward projected to generate the AC factor. The TGAC method was compared with measured AC (MAC) and calculated AC (CAC) methods using region of interest (ROI) and SPM analyses.Results: The ROI analysis showed that the activity of the TGAC EM PET images strongly correlated with those of the MAC data (y = 0.98x + 0.01, R(2) = 0.96). In addition, no significant difference was observed in the SPM analysis. By contrast, the CAC showed a significantly higher uptake in the deep gray regions compared to the MAC (corrected P < 0.05). The ROI correlation with MAC was worse than with the TGAC (R(2) = 0.84). In SPM analysis for the voxel-wise group comparisons between before and after the induction of deafness, only the TGAC showed equivalent results with the MAC.Conclusions: The TGAC was reliable in cat FDG brain PET studies in terms of compatibility with the MAC method. The TGAC might be a useful option for increasing study throughput and decreasing the probability of subject movement. In addition, it might reduce the possible biological effects of long-term anesthesia on the cat brain in investigations using animal-dedicated PET scanners. [ABSTRACT FROM AUTHOR]

Purpose: Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy. Methods: Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [18F]-fallypride, a high-affinity dopamine D2/3 receptor ligand. Parametric images of [18F]-fallypride specific binding were calculated using a reference tissue method, and the two groups were contrasted by whole-brain voxel-based analysis implemented in statistical parametric mapping(SPM5). Results: Dopamine D2/3 receptor availability was 27% lower in the bilateral anterior caudate-putamen of pilocarpine-treated rats as compared to controls (p < 0.05), but binding was unaffected in other striatal or extrastriatal regions. Conclusions: The finding of substantially reduced availability of dopamine D2/3 receptors in the anterior caudate-putamen of rats during the chronic phase of the pilocarpine model is in agreement with results of invasive (microinjection, microdialysis) animal studies that have revealed increased dopamine tonus and a D2/3 receptor-mediated anticonvulsant action of dopamine in the anterior segment of the rat striatum. The present PET approach could be prospectively applied for monitoring dopamine receptor changes longitudinally, that is, at different phases of the epileptogenic process, and opens perspectives for testing dopaminergic agents as potential antiepileptogenic drugs. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Biological image-guided radiotherapy aims at specifically irradiating biologically relevant sub-volumes within the tumor, as determined for instance by PET imaging. This approach requires that PET imaging be sensitive and specific enough to image various biological pathways of interest, e.g. tumor metabolism, proliferation and hypoxia. In this framework, a validation of PET imaging used for adaptive radiotherapy was undertaken in animal models by comparing small-animal PET images (2.7mm resolution) with autoradiography (AR) (100μm resolution) in various tumors under various physiological situations. Methods: A specific template for tumor-bearing mouse imaging has been designed (Christian, R&O, 2008). It allows for the registration between MRI images (Biospec, Bruker), FDG–PET images (Mosaic, Philips) and AR (FLA-5100, Fujifilm). After registration, the tumors on the PET and AR images were segmented using a threshold-based method. The thresholds were selected to obtain absolute equal volumes in the PET and AR images. Matching indexes were then calculated between the various volumes. The entire imaging process was performed for FSAII tumors (n =5), SCCVII (n =5) and irradiated (35Gy) FSAII tumors (n =5). Results: In regions with high FDG activity delineated using high value thresholds, low matching values of 39%±11% (mean±SD) were observed between the volumes delineated on the PET images and those delineated on AR. The matching values progressively increased when considering larger volumes obtained with lower thresholds. These findings were independent of tumor type, tumor metabolism or tumor size. The relationship between the matching values and the percentage of overall tumor volume was fitted through a power regression (r =0.93). As shown by simulations, the matching improved with higher PET resolution. The results can be extrapolated to human tumors imaged with a whole-body PET system. Conclusion: Discrepancies were found between the PET images and the underlying microscopic reality represented by AR images. These differences, attributed to the finite resolution of PET, were important when considering small and highly active regions of the tumors. Dose painting based on PET images should therefore be carefully considered and should take these limitations into account. [Copyright &y& Elsevier]

Improved spatial resolution without sacrificing sensitivity is one of the most challenging developmental goals for small animal PET scanners. The 3-layer configuration that we propose here utilizes relative offsets of half a crystal pitch in x- and y-directions, and pulse shape discrimination to obtain depth of interaction (DOI). Three layers of crystals with a dimension 1.5 x 1.5 x 7.0 mm3 were composed of a L0.2 GSO (Lu0.4 Gd1.6 SiO4: Ce) crystal layer and a L0.9 GSO (Lu1.8 Gd0.2 SiO4 Ce) crystal layer aligned with each other, and a L0.9 GSO crystal layer offset at half a crystal pitch in x- and y-directions. The L0.9 GSO crystal layer was attached to a Hamamatsu H9500 flat-panel PMT. The devised small animal PET scanner has a diameter of 84 mm with one detector ring, and can be upgraded to two detector rings. GEANT4 Monte-Carlo simulation was used to estimate sensitivities of ~12% and ~20%, respectively, at the center of one and two PMT ring system with an energy window of 350~750 keV. We present flood images with peak-to-valley ratios of about 5-6 obtained using 22Na and layer identification capability of ~99 % with pulse shape analysis, and verified the basic concepts of multi-layer small animal PET. [ABSTRACT FROM PUBLISHER]

To investigate whether [11C]PK-11195, a specific peripheral benzodiazepine receptors (PBRs) ligand for positron emission tomography (PET), can show activated microglia in a rat brain injury model. On day 1, ethanol was injected into the rat’s right striatum (ST) using a stereotaxic operative procedure. On day 3, head magnetic resonance imaging (MRI) scans for surgically treated rats were performed to evaluate ethanol injury morphologically. On day 4, dynamic PET scans (17 injured rats and 7 non-injured controls) were performed for 60 min with an animal PET scanner under chloral hydrate anesthesia following a bolus injection of [11C]PK-11195 through tail vein. Because PBRs are present throughout the brain, there is no suitable receptor-free reference region. The reference tissue model may not be applicable because of low target to background ratio for low affinity of [11C]PK-11195 to PBRs. We evaluated the PBRs binding with regions of interest (ROIs)-based approach to estimate total distribution volume ( V). We used an integral from 0 min to 60 min ( V 60) as an estimate of V. On the coronal PET image, ROIs were placed on bilateral ST. Differences in right/left ST V 60 ratios between lesioned and unlesioned control rats were compared using unpaired t tests. Immunohistochemical staining was performed for confirming the presence of activated microglia following decapitation on the PET experiment day. The right/left ST V 60 ratios in lesioned rats (1.07 ± 0.08) were significantly higher than those in unlesioned control rats (1.00 ± 0.06, P < 0.05). On immunohistochemical staining, activated microglia were exclusively observed in the injured right ST but not in the noninjured left ST of the injury rats and the bilateral ST of the non-injured control rats. These results suggest that [11C]PK-11195 PET imaging would be a useful tool for evaluating microglial activation in a rat brain injury model. [ABSTRACT FROM AUTHOR]

Abstract: An animal PET scanner using CdTe detectors was developed for the purpose of biomedical study using mice and rats. A spatial resolution of 0.8mm FWHM within the central 20mm-diameter of the field of view (FOV) was obtained by small CdTe elements of 1.1mm×5.0mm×1.0mm. This spatial resolution is the first achievement of a practical semiconductor animal PET scanner. The determination of the depth of the γ interaction in the detector was carried out by the use of two detector layers. The FOV is 64mm in diameter and 26mm in axis. Fine [18F]FDG images of the heads of a mouse and a rat, where the cerebral cortex, the gray matter and the corpus striatum could be respectively distinguished, were successfully obtained. This work inspires the dawn of the high resolution semiconductor PET scanner age as the next generation. [Copyright &y& Elsevier]

Abstract: Monte Carlo modelling is widely used in nuclear medicine for system optimization and for image processing in order to obtain system data that cannot be measured experimentally. Any simulation model should be validated, especially in terms of spatial resolution, count rates, scatter fraction and sensitivity in the case of positron emission tomography (PET) systems. The aim of this study was to compare the performance of a Mosaic animal PET system model to the real system by using raw data in a list-mode format, in order to preserve all the precision and accuracy of the acquired data. GATE package was used to design a realistic model of the Mosaic system. Detectors, shielding, cap, air medium, phantoms, sources and electronic processing were simulated in GATE. Sensitivity obtained from experimental and simulated data were compared using the list-mode data for different energy windows. Measurements of count rates were performed for uniform cylindrical phantoms for both mouse and rat. Output data were recorded with the same spatial sampling as the experimental data. Point spread functions at different locations in the field of view were analysed in raw and reconstructed formats. Simulated and measured sensitivity differed by less than 5%. Simulated and measured single and prompt count rates agreed within 6% for activities up to 100MBq for the two phantoms. A semi-empirical approach was used to simulate energy efficiency and losses of resolution after crystals interactions (detector blurring). Spatial resolution, assessed on simulated sinograms and on reconstructed data, agreed with real data. Comprehensive evaluation of the Monte Carlo modelling of a microPET system was performed using list-mode data and showed that the GATE model was appropriate to accurately reproduce the response of the system. [Copyright &y& Elsevier]

Objective: Detector designs for small animal scanners are currently dominated by discrete crystal implementations. However, given the small crystal cross-sections required to obtain very high resolution, discrete designs are typically expensive, have low packing fraction, reduced light collection, and are labor intensive to build. To overcome these limitations we have investigated the feasibility of using a continuous miniature crystal element (cMiCE) detector module for high resolution small animal PET applications. Methods: The detector module consists of a single continuous slab of LSO, 25×25 mm2 in exposed cross-section and 4 mm thick, coupled directly to a PS-PMT (Hamamatsu R5900-00-C12). The large area surfaces of the crystal were polished and painted with TiO2 and the short surfaces were left unpolished and painted black. Further, a new statistics based positioning (SBP) algorithm has been implemented to address linearity and edge effect artifacts that are inherent with conventional Anger style positioning schemes. To characterize the light response function (LRF) of the detector, data were collected on a coarse grid using a highly collimated coincidence setup. The LRF was then estimated using cubic spline interpolation. Detector performance has been evaluated for both SBP and Anger based decoding using measured data and Monte Carlo simulations. Results: Using the SBP scheme, edge artifacts were successfully handled. Simulation results show that the useful field of view (UFOV) was extended to ∼22×22 mm2 with an average point spread function of ∼0.5 mm full width of half maximum (FWHMPSF). For the same detector with Anger decoding the UFOV of the detector was ∼16×16 mm2 with an average FWHMPSP of ∼0.9 mm. Experimental results yielded similar differences between FOV and resolution performance. FWHMPSF for the SBP and Anger based method was 1.4 and 2.0 mm, uncorrected for source size, with a 1 mm diameter point source, respectively. Conclusion: A continuous detector module with an average FWHMPSF approaching one millimeter has been built and tested. Furthermore, the results demonstrate that our SBP scheme yields improved performance over traditional Anger techniques for our cMiCE detector. [Copyright &y& Elsevier]

The performance of a high resolution positron emission tomography (PET) system SHR-2000 for animal studies was re-evaluated six years after its installation. The system employs a detector array consisting of BGO crystals that are 1.7 mm (transaxially) by 10 mm (axially) by 30 mm (deep). A block detector, which is a position-sensitive photomultiplier tube (PMT) coupled to 4 arrays of BGO crystals has been adopted to the system. There are 15 block detectors positioned to form a 35 cm diameter ring with a field of view (FOV) of 17 cm by 4.6 cm axially, giving the system a 7 slice imaging capability. For six year workload in spatial resolution (FWHM), there were approximately a 2.6% increase at tangential FOV and a 7.5% increase at radial FOV. In axial resolution (FWHM) there was almost no change. The count rate loss for the true count rate increased 1.3% at 200 kBq/ ml. The average slice sensitivity showed a decrease of approximately 4.1%, and in scatters it showed an increase of approximately 1.4%. In animal experiments, the bones of guinea pigs were clearly identified with 18F fluoride ion. These experiments show that after a six year workload, the system also maintains good performance and has good stability. [ABSTRACT FROM AUTHOR]

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation–related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep. [ABSTRACT FROM AUTHOR]

Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68 Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to α v β 3 integrin receptors. The main objective of this study was to develop a method for 68 Ga-labeling of RGD containing bicyclic octapeptide ([ 68 Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [ 68 Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68 Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [ 68 Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis., Competing Interests: None.

Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle ( 89 Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89 Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89 Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89 Zr-NRep in tumors. 89 Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89 Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89 Zr-NRep.

Among noninvasive functional brain imaging techniques, (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has a comparative advantage in detecting active brain regions in freely locomoting animals. We developed an [(18) F]FDG-PET protocol that visualizes active brain regions that respond preferentially to citrate-induced multiple behaviors in freely locomoting rats. In addition, c-Fos immunohistochemistry, an activity-dependent mapping, was performed to examine whether the areas detected by PET correspond to regions with c-Fos-immunopositive neurons. Citrate (0.1 M) was intraorally applied to detect activated brain regions responding to gustation and the rejection behaviors including gaping and tongue protrusion, which would potently activate the limbic system. PET images during citrate stimulation were subtracted from those obtained during free locomotion or during application of distilled water. Citrate increased FDG signals in multiple gustation-related regions: the nucleus accumbens (core and shell), the ventromedial nucleus of the thalamus, the basolateral and central nuclei of the amygdala, the hypothalamus, and the insular cortex. In addition, the ventrolateral striatum and the cingulate and entorhinal cortices, which have received less attention in the field of gustatory studies, also showed an increase in FDG signals. As expected, c-Fos-immunopositive cells were also found in these regions, suggesting that increased FDG signals induced by intraoral citrate injection are likely to reflect neural activity in these regions. Our [(18) F]FDG-PET protocol reveals the contributions of multiple brain regions responding to aversive taste in freely locomoting rats, and this approach may aid in the identification of unknown neural networks especially relating to the limbic information processing., (Copyright © 2013 Wiley Periodicals, Inc.)