Heat Capacity Function, Enthalpy of Formation and Absolute Entropy of Mg(AlH4 )2.

In this investigation, we set out first to characterize the thermodynamics of Mg(AlH4 )2 and secondly to use the determined data to reevaluate and update existing estimation procedures for heat capacity functions, enthalpies of formation and absolute entropies of alanates. Within this study, we report the heat capacity function of Mg(AlH4 )2 in the temperature range from 2 K to 370 K and its enthalpy of formation and absolute entropy at 298.15 K, being - 70 . 6 ± 3 . 6 ${ - 70.6 \pm 3.6}$  kJ mol-1 and 133.06 J (K mol)-1 , respectively. Using these values, we updated and expanded methods for the estimation of thermodynamic data of alanates.

Study on the kinetics of the adsorption and desorption of NH3 on Fe/HBEA zeolite.

In this work, a Fe/HBEA zeolite (Si/Al: 12.5), representing an effective catalyst for the NH3-SCR process, was physico-chemically characterized and investigated regarding the kinetics of the adsorption and desorption of NH3. The sample was evaluated by N2 physisorption, 57Fe Möessbauer and DRUV-Vis spectroscopy, while the kinetics was investigated by temperature-programmed desorption of NH3 (TPD) including different adsorption temperatures. It was shown that the NH3 chemisorption results in weakly and strongly bonded molecular ammonia as well as ammonium species. A kinetic mean field model was developed implying two different types of adsorbates reflecting low (ca. 200 °C). Kinetic parameters and surface coverages were obtained from numeric fits of the TPD curves, whereas pre-exponential factors of adsorption were deduced from the kinetic gas theory. As a result, the activation energy for the NHx adsorbate decomposition in the low temperature regime, which is assigned to single and double bonded ammonium species was determined to be 106 kJ mol-1. The NH3 desorption at higher temperatures referred to an activation energy of 133 kJ mol-1 predominately related to NH3 coordinated to Lewis acid surface sites and to some extent to stabilized NH4+ species. For validation of the kinetic model, experiments were simulated including NH3 adsorption at different temperatures, subsequent flushing with N2 and final TPD. Additionally, the consistency of the activation energies with the thermodynamic data was checked using differential scanning calorimetry and a van't Hoff approach.

Synthesis and Properties of Branched Hydrogenated Nonasilanes and Decasilanes.

Branched higher silicon hydrides Si nH2 n+2 with n > 6 were recently found to be excellent precursors for the liquid phase deposition of silicon films. Herein we report the gram-scale synthesis of the novel nona- and decasilanes (H3Si)3Si(SiH2) nSi(SiH3)3 (2: n = 1, 5: n = 2) from (H3Si)3SiLi and Cl(SiPh2) nCl by a combined salt elimination/dephenylation/hydrogenation approach. Structure elucidation of the target molecules was performed by NMR spectroscopy and X-ray crystallography. 2 and 5 are nonpyrophoric and exhibit a bathochromically shifted UV absorption compared to neopentasilane and the structurally related octasilane (H3Si)3SiSi(SiH3)3. TG-MS analysis elucidated increased decomposition temperatures and decreased ceramic yields for branched hydrosilanes relative to cyclopentasilane. Otherwise, very similar thermal properties were observed for hydrosilane oligomers with linear and branched structures.

[18F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection.

Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment.IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.

Hydrogen absorption and desorption in the V-Al-H system.

The presented work sets out to investigate the influence of aluminium on the hydrogenation of vanadium by first studying the hydrogenation properties of the V-H system in detail followed by the study of the V-Al-H system. Aluminium was found to have a stabilising effect on vanadium hydride phases. Presumably by functioning as an oxygen getter, aluminium lowers equilibrium pressures and increases hydrogen capacities in respect to the V/H ratio compared to the V-H system. Attempts of the synthesis of the hypothetical V(AlH4)x by metathesis and direct hydrogenation were not successful, suggesting its instability below room temperature at ambient pressure as well as up to 180 bar of hydrogen pressure in the temperature range of 30 to 100 °C.

Longitudinal analyses using 18F-Fluorodeoxyglucose positron emission tomography with computed tomography as a measure of COVID-19 severity in the aged, young, and humanized ACE2 SARS-CoV-2 hamster models.

This study compared disease progression of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in three different models of golden hamsters: aged (≈60 weeks old) wild-type (WT), young (6 weeks old) WT, and adult (14-22 weeks old) hamsters expressing the human-angiotensin-converting enzyme 2 (hACE2) receptor. After intranasal (IN) exposure to the SARS-CoV-2 Washington isolate (WA01/2020), 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography with computed tomography (18F-FDG PET/CT) was used to monitor disease progression in near real time and animals were euthanized at pre-determined time points to directly compare imaging findings with other disease parameters associated with coronavirus disease 2019 (COVID-19). Consistent with histopathology, 18F-FDG-PET/CT demonstrated that aged WT hamsters exposed to 105 plaque forming units (PFU) developed more severe and protracted pneumonia than young WT hamsters exposed to the same (or lower) dose or hACE2 hamsters exposed to a uniformly lethal dose of virus. Specifically, aged WT hamsters presented with a severe interstitial pneumonia through 8 d post-exposure (PE), while pulmonary regeneration was observed in young WT hamsters at that time. hACE2 hamsters exposed to 100 or 10 PFU virus presented with a minimal to mild hemorrhagic pneumonia but succumbed to SARS-CoV-2-related meningoencephalitis by 6 d PE, suggesting that this model might allow assessment of SARS-CoV-2 infection on the central nervous system (CNS). Our group is the first to use (18F-FDG) PET/CT to differentiate respiratory disease severity ranging from mild to severe in three COVID-19 hamster models. The non-invasive, serial measure of disease progression provided by PET/CT makes it a valuable tool for animal model characterization.

Advances in Preclinical PET.

The classical intent of PET imaging is to obtain the most accurate estimate of the amount of positron-emitting radiotracer in the smallest possible volume element located anywhere in the imaging subject at any time using the least amount of radioactivity. Reaching this goal, however, is confounded by an enormous array of interlinked technical issues that limit imaging system performance. As a result, advances in PET, human or animal, are the result of cumulative innovations across each of the component elements of PET, from data acquisition to image analysis. In the report that follows, we trace several of these advances across the imaging process with a focus on small animal PET.

A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients.

PURPOSE: The primary aim of this study was to investigate the pharmacokinetics of 18F-DCFPyL, an 18F-labeled PSMA-based ligand, and to explore the utility of early time point positron emission tomography (PET) imaging extracted from PET data to distinguish malignant primary prostate from benign prostate tissue. PROCEDURES: Ten consecutive patients with biopsy-proven high-risk prostate cancer underwent a dynamic 18F-DCFPyL PET/CT scan of the pelvis for the first 45 min post-injection (p.i.) followed by a static PET/CT at 2 h p.i. 18F-DCFPyL uptake values and kinetics were compared between benign prostate tissue and prostate cancer, including quantitative pharmacokinetic PET parameters extracted from 18F-DCFPyL time activity curves generated from dynamic data using a two-tissue compartment model and Patlak plots. RESULTS: 18F-DCFPyL uptake values were significantly higher in primary prostate tumors than those in benign prostatic hyperplasia (BPH) and normal prostate tissue at 5 min, 30 min, and 120 min p.i. (P = 0.0002), when examining both SUVmax and SUVmean values. The two-tissue compartment model found an overall influx value (Ki) of 0.063 in primary prostate cancer, demonstrating a Ki over 15-fold higher in malignant prostate tissue compared with BPH (Ki = 0.004) and normal prostate tissue (Ki = 0.005) (P = 0.0001). CONCLUSION: High-risk primary prostate cancer is readily identified on dynamic and static, delayed, 18F-DCFPyL PET images. The tumor-to-background ratio increases over time, with optimal 18F-DCFPyL PET/CT imaging at 120 min p.i. for evaluation of prostate cancer, but not necessarily ideal for clinical application. Primary prostate cancer demonstrates different uptake kinetics in comparison to BPH and normal prostate tissue. The 15-fold difference in Ki between prostate cancer and non-cancer (BPH and normal) tissues translates to an ability to distinguish prostate cancer from normal tissue at time points as early as 5 to 10 min p.i.

Intramuscular [18F]F-FDG Administration for Successful PET Imaging of Golden Hamsters in a Maximum Containment Laboratory Setting.

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [18F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time-activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [18F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [18F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting.

68Ga-DOTA-affibody molecule for in vivo assessment of HER2/neu expression with PET.

PURPOSE: Overexpression of HER2/neu in breast cancer is correlated with a poor prognosis. It may vary between primary tumors and metastatic lesions and change during the treatment. Therefore, there is a need for a new means to assess HER2/neu expression in vivo. In this work, we used (68)Ga-labeled DOTA-Z(HER2:2891)-Affibody to monitor HER2/neu expression in a panel of breast cancer xenografts. METHODS: DOTA-Z(HER2:2891)-Affibody molecules were labeled with (68)Ga. In vitro binding was characterized by a receptor saturation assay. Biodistribution and PET imaging studies were conducted in athymic nude mice bearing subcutaneous human breast cancer tumors with three different levels of HER2/neu expression. Nonspecific uptake was analyzed using non-HER2-specific Affibody molecules. Signal detected by PET was compared with ex vivo assessment of the tracer uptake and HER2/neu expression. RESULTS: The (68)Ga-DOTA-Z(HER2:2891)-Affibody probe showed high binding affinity to MDA-MB-361 cells (K (D) = 1.4 ± 0.19 nM). In vivo biodistribution and PET imaging studies demonstrated high radioactivity uptake in HER2/neu-positive tumors. Tracer was eliminated quickly from the blood and normal tissues, resulting in high tumor-to-blood ratios. The highest concentration of radioactivity in normal tissue was seen in the kidneys (227 ± 14%ID/g). High-contrast PET images of HER2/neu-overexpressing tumors were recorded as soon as 1 h after tracer injection. A good correlation was observed between PET imaging, biodistribution estimates of tumor tracer concentration, and the receptor expression. CONCLUSION: These results suggest that PET imaging using (68)Ga-DOTA-Z(HER2:2891)-Affibody is sensitive enough to detect different levels of HER2/neu expression in vivo.

High-separation performance of chromatographic capillaries coated with MOF-5 by the controlled SBU approach.

Recently developed MOF surface-coating techniques, the controlled SBU approach (CSA) for the generation of MOF-5, and the use of self-assembled monolayers have been combined to generate a wall-bonded, crosslinked stationary phase for gas chromatographic capillary columns displaying excellent performance in the separation of natural gas components. The chromatographic performance of this new type of column has been compared to the state-of-the-art solution for this separation problem, namely a coated silica column of the porous layer open tubular (PLOT) type. Chromatographic parameters such as separation, resolution, and tailing factors, as well as plate numbers and heights in the case of isothermal operation, have been determined. Kinetic and thermodynamic parameters characterizing the analyte-stationary phase interaction have been determined for various C1-C4 analytes.

Sodium Fluoride-18 and Radium-223 Dichloride Uptake Colocalize in Osteoblastic Mouse Xenograft Tumors.

Background: Patients with osteoblastic bone metastases are candidates for radium-223 (223RaCl2) therapy and may undergo sodium fluoride-18 (18F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. 18F-NaF has been shown to predict 223RaCl2 uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of 18F-NaF and 223RaCl2 in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. Materials and Methods: 18F-NaF and 223RaCl2 were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. Results: 18F and 223Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r2 = 0.82) and in microcalcified regions within these tumors (r2 = 0.87). Intratumor distributions of 18F and 223Ra were spatially congruent in these microcalcified regions. Conclusions: 18F-NaF and 223RaCl2 uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of 18F is predictive of 223Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered 223Ra dose and therapeutic effect.

Experimental evaluation of depth-of-interaction correction in a small-animal positron emission tomography scanner.

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling.

Positron emission tomography for serial imaging of the contused adult rat spinal cord.

We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was exposed by laminectomy and subsequently contused using the Infinite Horizon impactor (Precision System and Instrumentation, Lexington, KY) at 225 kDyn. In control rats (n = 4), the T9 spinal cord was exposed by laminectomy but not contused. At 0.5 hours and 3, 7, and 21 days postinjury, 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) was given intravenously followed 1 hour later by sequential PET and CT. Regions of interest (ROIs) at T9 (contused) and T6 (uninjured) spinal cord segments were manually defined on CT images and aided by fiduciary markers superimposed onto the coregistered PET images. Monte Carlo simulation revealed that about 33% of the activity in the ROIs was due to spillover from adjacent hot areas. A simulation-based partial-volume compensation (PVC) method was developed and used to correct for this spillover effect. With PET-CT, combined with PVC, we were able to serially measure standardized uptake values of the T9 and T6 spinal cord segments and reveal small, but significant, differences. This approach may become a tool to assess the efficacy of spinal cord repair strategies.

A Study of 219Rn Outgassing and 211Pb Contamination from 223Ra In dry, Liquid, and Murine Tissue Samples.

INTRODUCTION: A study of Pb contamination caused by the outgassing of Rn from Ra in dry, liquid, and murine tissues samples has been made to help design proper handling procedures for Ra in preclinical biodistribution work. MATERIALS AND METHODS: Pb activity levels were measured from Ra in dry, liquid, and tissue samples using aspiration and autoradiography techniques. RESULTS: Using aspiration techniques on dry samples of Ra, an average Rn outgassing rate of 51% ± 21% was measured with one measurement reaching as high as 81%. 31% ± 4% Pb contamination was measured within a 4.3 cm radius of a dry Ra source placed inside a 10-cm-diameter petri dish where the lip of the petri dish contained the Rn dissemination. Without the containment of the petri dish, Rn can reach as far as 7.8 cm from the source with trace levels spreading further. Using aspiration techniques on liquid samples of Ra, outgassing rates of Rn were 0.9% ± 0.3%. The outgassing levels in harvested organs from a biodistribution were as high as 10.1% ± 0.4% for an intraperitoneally injected mouse and 0.204% ± 0.006% for an intravenously injected mouse. The outgassing of the intravenously injected mouse carcass was less than 0.1%. CONCLUSION: In dry form, the high levels of Rn outgassing from a Ra source necessitate the use of ventilated biohoods when handling or preparing dry Ra from source vials. The very low levels of Rn outgassing from Ra liquid sources reduces exposure to Rn by a factor of 50. Rn exposure from murine organ tissue reaches levels of 10% when handling organs from an intraperitoneal injection and less than 0.2% for an intravenous injection.

Dual-modality molecular imaging using antibodies labeled with activatable fluorescence and a radionuclide for specific and quantitative targeted cancer detection.

Multimodality molecular imaging should have potential for compensating the disadvantages and enhancing the advantages of each modality. Nuclear imaging is superior to optical imaging in whole body imaging and in quantification due to good tissue penetration of gamma rays. However, target specificity can be compromised by high background signal due to the always signal ON feature of nuclear probes. In contrast, optical imaging can be superior in target-specific imaging by employing target-specific signal activation systems, although it is not quantitative because of signal attenuation. In this study, to take advantage of the mutual cooperation of each modality, multimodality imaging was performed by a combination of quantitative radiolabeled probe and an activatable optical probe. The monoclonal antibodies, panitumumab (anti-HER1) and trastuzumab (anti-HER2), were labeled with 111In and ICG and tested in both HER1 and HER2 tumor bearing mice by the cocktail injection of radiolabeled and optical probes and by the single injection of a dual-labeled probe. The optical and nuclear images were obtained over 6 days after the conjugates injection. The fluorescence activation properties of ICG labeled antibodies were also investigated by in vitro microscopy. In vitro microscopy demonstrated that there was no fluorescence signal with either panitumumab-ICG or trastuzumab-ICG, when the probes were bound to cell surface antigens but were not yet internalized. After the conjugates were internalized into the cells, both conjugates showed bright fluorescence signal only in the target cells. These results show that both conjugates work as activatable probes. In in vivo multimodality imaging by injection of a cocktail of radio-optical probes, only the target specific tumor was visualized by optical imaging. Meanwhile, the biodistribution profile of the injected antibody was provided by nuclear imaging. Similar results were obtained with radio and optical dual-labeled probes, and it is confirmed that pharmacokinetic properties did not affect the results above. Here, we could characterize the molecular targets by activatable optical probes and visualize the delivery of targeting molecules quantitatively by radioactive probes. Multimodality molecular imaging combining activatable optical and radioactive probes has great potential for simultaneous visualization, characterization, and measurement of biological processes.

Hyperbranched PEI with various oligosaccharide architectures: synthesis, characterization, ATP complexation, and cellular uptake properties.

We present a rapid synthetic method for the development of hyperbranched PEIs decorated with different oligosaccharide architectures as carrier systems (CS) for drugs and bioactive molecules for in vitro and in vivo experiments. Reductive amination of hyperbranched PEI with readily available oligosaccharides results in sugar functionalized PEI cores with oligosaccharide shells of different densities. These core-shell architectures were characterized by NMR spectroscopy, elemental analysis, SLS, DLS, IR, and polyelectrolyte titration experiments. ATP complexation of theses polycations was examined by isothermal titration calorimetry to evaluate the binding energy and ATP/CS complexation ratios under physiological conditions. In vitro experiments showed an enhanced cellular uptake of ATP/CS complexes compared to those of the free ATP molecules. The results arise to initiate further noncovalent complexation studies of pharmacologically relevant molecules that may lead to the development of therapeutics based on this polymeric delivery platform.

N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine, [18F]DCFBC: a new imaging probe for prostate cancer.

PURPOSE: Previously, we showed successful imaging of xenografts that express the prostate-specific membrane antigen (PSMA) using small-animal positron emission tomography (PET) and the radiolabeled PSMA inhibitor N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[11C]methyl-l-cysteine. Herein, we extend that work by preparing and testing a PSMA inhibitor of the same class labeled with fluorine-18. EXPERIMENTAL DESIGN: N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-l-cysteine ([18F]DCFBC) was prepared by reacting 4-[18F]fluorobenzyl bromide with the precursor (S)-2-[3-[(R)-1-carboxy-2-mercaptoethyl]ureido]-pentanedioic acid in ammonia-saturated methanol at 60 degrees C for 10 min followed by purification using C-18 reverse-phase semipreparative high-performance liquid chromatography. Severe combined immunodeficient mice bearing a s.c. PSMA+ PC-3 PIP tumor behind one shoulder and a PSMA(-) PC-3 FLU tumor behind the other shoulder were injected via the tail vein with either 1.85 MBq (50 microCi) of [18F]DCFBC for ex vivo biodistribution or 7.4 MBq (200 microCi) for imaging. For biodistribution, mice were sacrificed at 5, 15, 30, 60, and 120 min. Tumor, blood, and major organs were harvested and weighed, and radioactivity was counted. Imaging was done on the GE eXplore Vista small-animal PET scanner by collecting 12 consecutive 10-min frames. RESULTS: Radiochemical yield for [18F]DCFBC averaged 16 +/- 6% (n = 8) from 4-[18F]fluorobenzyl bromide. Specific radioactivities ranged from 13 to 133 GBq/micromol (350-3,600 Ci/mmol) with an average of 52 GBq/micromol (1,392 Ci/mmol; n = 6). Biodistribution and imaging studies showed high uptake of [18F]DCFBC in the PIP tumors with little to no uptake in FLU tumors. High radiopharmaceutical uptake was also seen in kidneys and bladder; however, washout of radioactivity from these organs was faster than from the PIP tumors. The maximum PIP tumor uptake was 8.16 +/- 2.55% injected dose per gram, achieved at 60 min after injection, which decreased to 4.69 +/- 0.89 at 120 min. The PIP tumor to muscle ratio was 20 at 120 min after injection. Based on the mouse biodistribution, the dose-limiting organ is the kidneys (human estimated absorbed dose: 0.05 mGy/MBq; 0.2 rad/mCi). CONCLUSION: [18F]DCFBC localizes to PSMA+-expressing tumors in mice, permitting imaging by small-animal PET. This new radiopharmaceutical is an attractive candidate for further studies of PET imaging of prostate cancer.

The Distribution Volume of 18F-Albumin as a Potential Biomarker of Antiangiogenic Treatment Efficacy.

Objective: 18F-albumin, a vascular imaging agent, may have potential to assess tumor responses to anti-angiogenic therapies. In these studies tumor distribution volume of 18F-albumin were first determined in various human tumor xenografts from biodistribtuion measurments and then one of the tumor type was used to evaluate changes in 18F-albumin uptake in anti-angiognic tumor model. Method: 18F-albumin was synthesized via conjugation of 6-[18F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18F]F-Py-TFP, with rat albumin. From the biodistribution of 18F-albumin in various human tumor xenografts tumor distribution volumes (DVs; tumor%ID/g:blood%ID/g) were first determined at various time points. Then, the ability of 18F-albumin to detect tumor angiogenic inhibition in one of these tumor types (U87MG) following treatment with sunitinib was evaluated by position emission tomography (PET) imaging at 0, 7, 14, and 21 days post treatment. Caliper measurements of tumor dimensions were also made at these same times. At Day 21, following imaging, biodistributions, autoradiography of tumor tissues and tumor blood vessel counts (CD31 IHC) were performed. Results: 18F-albumin retention in various tumors steadily increased over time with U87MG tumor exhibiting the highest uptake (DV) at all times. Significant decreases in 18F-albumin DVs were observed one week post-treatement (-39%) vs. controls whereas tumor caliper volumes were not significantly decreased until days 14 and 21. At day 21 the significant decrease in DVs in the treatment group (-44%) paralleled biodistribution DV measurements and was consistent with autoradiography and CD31 IHC findings. Conclusion: These data suggest that 18F-albumin DVs obtained by imaging may serve as an early biomarker of the effectiveness of anti-angiogenic therapy and thus aid in patient management and treatment planning.

One-pot synthesis and biodistribution of fluorine-18 labeled serum albumin for vascular imaging.

INTRODUCTION: Equilibrium single-photon radionuclide imaging methods for assessing cardiac function and the integrity of the vascular system have long been in use for both clinical and research purposes. However, positron-emitting blood pool agents that could provide PET equivalents to these (and other) clinical procedures have not yet been adopted despite technical imaging advantages offered by PET. Our goal was to develop a PET blood pool tracer that not only meets necessary in vivo biological requirements but can be produced with an uncomplicated and rapid synthesis method which would facilitate clinical translation. Herein, albumin labeled with fluorine-18 was synthesized using a one-pot method and evaluated in vitro and in vivo in rats. METHODS: A ligand (NODA-Bz-TFPE), containing NODA attached to a tetrafluorophenylester (TFPE) via a phenyl linker (Bz), was labeled with aluminum fluoride (Al[18F]F). Conjugation of the serum albumin with the ligand (Al[18F]F-NODA-Bz-TFPE), followed by purification (size exclusion chromatography), yielded the final product (Al[18F]F-NODA-Bz-RSA/HSA). In vitro stability was evaluated in human serum albumin by HPLC. Rat biodistributions and whole-body PET imaging over a 4 h time course were used for the in vivo evaluation. RESULTS: This synthesis exhibited an overall radiochemical yield of 45 ±â€¯10% (n = 30), a 50-min radiolabeling time, a radiochemical purity >99% and apparent stability up to 4 h in human serum. Blood had the highest retention of Al[18F]F-NODA-Bz-RSA at all times with a blood half-life of 5.2 h in rats. Al[18F]F-NODA-Bz-RSA distribution in most rat tissues remained relatively constant for up to 1 h, indicating that the tissue radioactivity content represents the respective tissue plasma volume. Dynamic whole-body PET images were in agreement with these findings. CONCLUSIONS: A new ligand has been developed and radiolabeled with Al[18F]F that allows rapid (50-min) preparation of fluorine-18 serum albumin in one-pot. In addition to increased synthetic efficiency, the construct appears to be metabolically stable in rats. This method could encourage wider use of PET to quantify cardiac function and tissue vascular integrity in both research and clinical settings.