Evaluation of 18F-PSMA-1007 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy.

PURPOSE: Prostate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of 18F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence. METHODS: 71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01-67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq 18F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of 18F-PSMA-1007 were evaluated. RESULTS: 56 (79%) patients showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7-10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51-1.0, 1.1-2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001). CONCLUSION: 18F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients.

Mid-infrared multispectral confocal microscope using off-axis parabolic mirrors to study epiretinal membranes.

Mid-infrared (mid-IR) multispectral microscopy, especially operating at the wavelength of 5-11 µm, is an effective tool for detecting, identifying, and quantifying the structure and composition of biological tissues. Compared with that based on the optical lens, the mid-infrared microscope composed of off-axis parabolic (OAP) mirrors is low cost, simple, and suitable for longer range of wavelength without chromatic aberrations, while keeping the optical transmission efficiency. Here we report a compact and versatile mid-infrared multispectral confocal microscope based on off-axis parabolic mirrors. We also perform numerical calculations based on the vectorial diffraction theory on OAP mirrors and analyze the typical aberrations and misalignment of the OAP-based optical system. Finally, we perform multispectral imaging of the epiretinal membrane of the human eyes with the spectrum selected according to its resonance absorption peak. The system is designed to perform multispectral or even hyperspectral imaging to identify and predict potential disease.

FAPI-04 PET/CT Using [18F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient.

68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was 49.41 ± 3.19 GBq/µmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.

Quick Automatic Synthesis of Solvent-Free 16α-[18F] Fluoroestradiol: Comparison of Kryptofix 222 and Tetrabutylammonium Bicarbonate.

Estrogen receptor (ER) expression level of human breast cancer often reflects the stage of disease and is usually monitored by immunohistochemical staining in vitro. The preferable non-invasive and real-time diagnosis in vivo is more accessible by PET scan using 16α-[18F]FES. The objective of this study was to develop a quick automatic method for synthesis of solvent-free 16α-[18F]FES using a CFN-MPS-200 synthesis system and compare the catalytic efficiency of two phase transfer catalysts, Kryptofix 222/K2CO3 (K222/K2CO3) and tetrabutylammonium hydrogen carbonate (TBA·HCO3). In this method, phase transfer catalysts K222/K2CO3 and TBA·HCO3 were used, respectively. The intermediate products were both hydrolyzed with hydrochloric acid and neutralized with sodium bicarbonate. The crude product was purified with semi-preparative HPLC, and the solvent was removed by rotary evaporation. The effects of radiofluorination temperature and time on the synthesis were also investigated. Radiochemical purity of solvent-free product was above 99% and the decay-corrected radiochemical yield of 16α-[18F]FES was obtained in 48.7 ± 0.95% (catalyzed by K222/K2CO3, n = 4) and 46.7 ± 0.77% (catalyzed by TBA·HCO3, n = 4, respectively). The solvent-free 16α-[18F]FES was studied in clinically diagnosed breast cancer patients, and FES-PET results were compared with pathology diagnosis results to validate the diagnosis value of 16α-[18F]FES. The new method was more reliable, efficient, and time-saving. There was no significant difference in catalytic activity between K222/K2CO3 and TBA·HCO3.

Transplantable Carbonaceous Li+ Filtrating Membrane for Lithium Metal Protection.

Utilization of the lithium (Li) metal anode is seriously prevented by the undesirable side reactions with electrolyte solvents due to their mismatched energy gaps and easily lacerated SEI layer. In this work, we develop a transplantable carbonaceous membrane with a particular ability of filtrating Li+ ions by blocking organic solvents and use it as an independent protective component to isolate lithium metal anode from the electrolytes. This graphene-supported N-doped membrane (GNM) can separate organic carbonates of dimethyl carbonate (DMC) and diethyl carbonate (DEC) from H2O-DMC/DEC mixtures by holding back the organic solvents. When this membrane is used in a Li-Cu cell, a high Li Coulombic efficiency (CE) of 98.5% is maintained in carbonate electrolyte over 400 cycles. Application of GNM in Li-O2 full cell provides a sustainable use of Li metal for more than 200 cycles (2000 h) by keeping its shiny metal luster. Our results demonstrate that the use of an independent component with Li+ filtrating ability, such as the transplantable membrane of GNM developed in this work, should be a feasible remedy to protect Li metal anode in practical Li metal batteries.

Seed-Free Selective Deposition of Lithium Metal into Tough Graphene Framework for Stable Lithium Metal Anode.

Graphene has been wildly used as a host to suppress dendrite growth to stabilize the lithium metal anode. However, the high overpotential of lithium deposition on pure graphene has to be lowered by doping or employing precious metals. Additionally, the soft nature of graphene rendered itself to aggregate, consequently squeezing room for lithium accommodation. Herein, a tough graphene framework composed of 3D periodic hollow spheres was reported as a free-standing host to stabilize lithium metal anodes. The prepared 3D periodic hollow structure not merely reinforces the framework to maintain hollow structure under pressure caused by assembling battery, but also lowers the overpotential without the help of dopant or precious metals. It is worthy to note that high efficiency of ion diffusion, thanks to the channels interconnecting hollow spheres by holes on the walls, benefits both suppression of lithium dendrite and rate capability. The properties of low density and high mechanical strength make graphene frameworks electrode a promising lightweight Li host material, which reveals a new avenue for designing high-energy density electrode materials.

Prolonging the Cycle Life of a Lithium-Air Battery by Alleviating Electrolyte Degradation with a Ceramic-Carbon Composite Cathode.

Carbon materials with a high specific surface area are usually preferred to construct the air cathode of lithium-air batteries due to their abundant sites for oxygen reduction and discharge product growth. However, the high surface area also amplifies electrolyte degradation during charging, which would become the threshold of cyclability after addressing the issue of electrode passivation and pore clogging, but is usually overlooked in relevant research. Herein, it is proven that the critical influence of cathode surface area on electrolyte consumption by adopting carbon-ceramic composites to reduce the surface area of the air cathode. After screening several potential ceramic materials, an optimal composite of Ketjenblack (KB) and La0.7 Sr0.3 MnO3 (LSM) delivered a discharge capacity that was even higher than that of pure KB. This composite effectively mitigated the parasitic reaction current by 45 % if polarized at 4.4 V versus Li+ /Li. Correspondingly, this composite prolonged the cycle life of the cell by 156 %. The results demonstrate that electrolyte consumption during charging is one of the critical boundary conditions to restrain the cyclic stability of lithium-air batteries.

Application of Near-Infrared Optical Feedback Cavity Enhanced Absorption Spectroscopy (OF-CEAS) to the Detection of Ammonia in Exhaled Human Breath.

The qualitative and quantitative analysis to trace gas in exhaled human breath has become a promising technique in biomedical applications such as disease diagnosis and health status monitoring. This paper describes an application of a high spectral resolution optical feedback cavity enhanced absorption spectroscopy (OF-CEAS) for ammonia detection in exhaled human breath, and the main interference of gases such as CO2 and H2O are approximately eliminated at the same time. With appropriate optical feedback, a fibered distributed feedback (DFB) diode laser emitting at 1531.6 nm is locked to the resonance of a V-shaped cavity with a free spectral range (FSR) of 300 MHz and a finesse of 14,610. A minimum detectable absorption coefficient of αmin = 2.3 × 10-9 cm-1 is achieved in a single scan within 5 s, yielding a detection limit of 17 ppb for NH3 in breath gas at low pressure, and this stable system allows the detection limit down to 4.5 ppb when the spectra to be averaged over 16 laser scans. Different from typical CEAS with a static cavity, which is limited by the FSR in frequency space, the attainable spectral resolution of our experimental setup can be up to 0.002 cm-1 owing to the simultaneous laser frequency tuning and cavity dither. Hence, the absorption line profile is more accurate, which is most suitable for low-pressure trace gas detection. This work has great potential for accurate selectivity and high sensitivity applications in human breath analysis and atmosphere sciences.

Timing and optimized acquisition parameters for the whole-body imaging of ¹77Lu-EDTMP toward performing bone pain palliation treatment.

OBJECTIVES: Lutetium-177-labeled ethylenediamine-N,N,N',N'-tetrakis (methylene phosphonic acid) (¹77Lu-EDTMP), a beta-emitting bone-seeking therapeutic radiopharmaceutical being assessed as an agent for palliation of bone pain, can emit suitable gamma-photons for scintigraphy. This investigation sought to characterize its optimal conditions for whole-body gamma camera imaging in patients. MATERIALS AND METHODS: Eleven patients with bone metastases underwent whole-body bone scanning using both 99mTc-methyl-diphosphonate (99mTc-MDP) and ¹77Lu-EDTMP (29.4 ± 12.5 MBq/kg BW) utilizing a dual-head camera. For lutetium-177 imaging, two types of collimators, low-energy high-resolution (LEHR) and medium-energy general-purpose (MEGP), and two different peak energies of 113 and 208 keV were used. RESULTS: The femur-to-muscle uptake ratio (F/M) of 99mTc-MDP was 2.69 ± 1.06. For ¹77Lu-EDTMP, the significantly highest F/Ms were found at 24 h (12.59 ± 5.73) and 48 h (12.54 ± 5.23) by applying MEGP collimators and collecting the 208 keV photons. In all the combinations of collimator and peak energy, the F/Ms at 24 and 48 h are significantly higher than those at 1 h, except the combination of LEHR collimator and 208 keV peak energy. Lesion-to-normal bone uptake ratios of the 99mTc-MDP bone scan and images at the 24 and the 48-h phases of Lu-EDTMP were analyzed. MEGP and 208 keV had significantly higher values in lesion-to-normal bone uptake ratios. The combination of LEHR and 208 keV provided the poorest images. CONCLUSION: ¹77Lu-EDTMP can provide fine whole-body images with the best results when applying medium-energy collimation and collecting the 208 keV energy photons and alternatively by collecting both 208 and 113 keV photons for higher count statistics. The most appropriate time point for imaging is around 24 h after injection.

[Radiosynthesis of peripheral benzodiazepine receptor radioligand [N-methyl-(11)C]PK 11195 as an imaging agent for positron emission tomography].

OBJECTIVE: To establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product. METHODS: (11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied. RESULTS: (11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice. CONCLUSION: The (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.