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Preclinical evaluation of [ <sup>18</sup> F]MA3, a CB <sub/>2</sub> receptor agonist radiotracer for Positron Emission Tomography
摘要： Background and Purpose: Non-invasive in vivo imaging of CB2 receptors (CB2R) using positron emission tomography (PET) is pursued to study neuroinflammation. The purpose of this study is to evaluate the in vivo binding specificity of [18F]MA3, a CB2R agonist, in a rat model with local overexpression of human CB2R (hCB2R). Methods: [18F]MA3 was produced with good radiochemical yield and radiochemical purity. The radiotracer was evaluated in rats with local overexpression of hCB2R and in a healthy non-human primate using PET. Key results: Ex vivo autoradiography demonstrated CB2 specific binding of [18F]MA3 in rat hCB2R vector injected striatum. In a PET study, increased tracer binding in the hCB2R vector injected striatum compared to the contralateral control vector injected striatum was observed. Binding in hCB2R vector injected striatum was blocked with a structurally non related CB2R inverse agonist and a displacement study confirmed the reversibility of tracer binding. This study identified the utility of mutated inactive vector model for evaluation of CB2R agonist PET tracers. [18F]MA3 PET scans in the non-human primate showed good uptake and fast wash out from brain, but no CB2 specific binding was observed. Conclusion and Implications: Evaluation of [18F]MA3 in a rat model with local overexpression of hCB2R showed CB2 specific and reversible tracer binding. [18F]MA3 showed good brain uptake and subsequent wash out in a healthy non-human primate but no specific binding was observed. Further clinical evaluation of [18F]MA3 in patients with neuroinflammation is warranted.
关键词： CB2R,PET imaging,neuroinflammation,[18F]MA3,radiotracer
更新于2025-09-23 15:22:29
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Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]
摘要： Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. Acronym: PSMA-SRT Phase 3 trial.
关键词： Randomized phase 3 trial,PET/CT,Prostate cancer,PSMA,Salvage radiation therapy
更新于2025-09-23 15:22:29
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Performance characteristics of the digital Biograph Vision PET/CT system
摘要： This study evaluates the performance of the Siemens Biograph Vision digital PET/CT system (Siemens Healthineers, Knoxville, USA) according to the NEMA NU 2‐2012 standard (published by the National Electrical Manufacturers Association (NEMA)) to allow for a reliable, reproducible, and inter‐system comparable performance measurement. Methods: The new digital PET/CT features silicon photomultiplier (SiPM)‐based detectors with 3.2 mm lutetium oxyorthosilicate (LSO) crystals and full coverage of the scintillator area. The PET components incorporate eight rings of 38 detector blocks and each block contains 4x2 mini‐blocks. Each mini‐block consists of a 5x5 LSO‐array of 3.2x3.2x20 mm crystals coupled to a SiPM‐array of 16x16 mm, resulting in an axial field of view (FOV) of 26.1 cm. In this study PET/CT system performance will be evaluated conform the NEMA NU 2‐2012 standard with additional measurements described in the new NEMA NU 2‐2018 standard. Spatial resolution, sensitivity, count‐rate performance, accuracy of attenuation and scatter correction, Time‐of‐Flight (TOF) performance, and image quality will be determined. Measurements will be directly compared to results from its predecessor, the Biograph mCT Flow, using existing literature. Moreover, feasibility to comply with the European Association of Nuclear Medicine (EANM) Research Ltd (EARL) criteria will be evaluated and some illustrative patient PET images will be shown. Results: The Biograph Vision shows a transverse (resp. axial) spatial resolution at Full Width Half Maximum (FWHM) of 3.6 mm (resp. 3.5 mm) at 1 cm offset of the center of the FOV (measured with a 22Na 0.25 mm point‐source), a NEMA sensitivity of 16.4 kcps/MBq, and a NEMA peak NECR of 306 kcps at 32 kBq/mL. TOF resolution varied from 210 to 215 as count‐rate increased up to the peak NECR. The overall image contrast seen with the NEMA image quality phantom ranged from 77.2% to 89.8%. Furthermore, the system was able to comply with the current and future EARL performance criteria. Conclusions: The Biograph Vision outperforms the analog Biograph mCT Flow and the system is able to meet European harmonizing performance standards.
关键词： PET/CT,Digital detectors,NEMA,performance evaluation
更新于2025-09-23 15:22:29
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Development and <i>in vivo</i> evaluation of a novel kappa opioid receptor agonist as PET radiotracer with superior imaging characteristics
摘要： Studies have shown kappa opioid receptor (KOR) abnormalities in addictive disorders, other central nervous system diseases and Alzheimer’s disease. We have developed the first set of agonist 11C-GR103545 and antagonist 11C-LY2795050 radiotracers for positron emission tomography imaging of KOR in human. Nonetheless, 11C-GR103545 displays protracted uptake kinetics and is not an optimal radiotracer. Here we report the development and evaluation of 11C-EKAP and its comparison with 11C-GR103545. Methods: EKAP was synthesized and assayed for in vitro binding affinities, then radiolabeled with 11C-CH3OTf. PET studies were carried out in rhesus monkeys. Blocking studies were performed with naloxone and the selective KOR antagonists LY2795050 and LY2456302. Arterial input functions were generated for use in kinetic modeling. Brain time-activity curves were analyzed with the multilinear analysis 1 (MA1) method to derive binding parameters. Results: EKAP has high KOR affinity (Ki = 0.28 nM) and good selectivity in vitro. 11C-EKAP was prepared in good radiochemical purity. 11C-EKAP rapidly metabolized in plasma, and displayed fast and reversible kinetics in brain with peak uptake at < 20 min post-injection. Pre-blocking with naloxone (1 mg/kg) or LY2795050 (0.2 mg/kg) produced 84-89% receptor occupancy, while LY2456302 (0.05 & 0.3 mg/kg) dose-dependently reduced 11C-EKAP specific binding, thus demonstrating its binding specificity and selectivity in vivo. Mean MA1-derived BPND values were 1.74, 1.79, 1.46, 0.80 and 0.77 for cingulate cortex, globus pallidus, insula, striatum and frontal cortex, consistent with the known KOR distribution in primate brains. Conclusions: We have successfully developed 11C-EKAP as a novel KOR agonist tracer with dual attractive imaging properties of fast uptake kinetics and high specific binding in vivo.
关键词： 11C-EKAP,PET radiotracer,agonist,non-human primates,kappa opioid receptor
更新于2025-09-23 15:22:29
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Design study of dedicated brain PET with polyhedron geometry
摘要： BACKGROUND: Despite being the conventional choice, whole body PET cameras with a 76 cm diameter ring are not the optimal means of human brain imaging. OBJECTIVE: In fact, a dedicated brain PET with a better geometrical structure has the potential to achieve a higher sensitivity, a higher signal-to-noise ratio, and a better imaging performance. METHODS: In this study, a polyhedron geometrical dedicated brain PET (a dodecahedron design) is compared to three other candidates via their geometrical ef?ciencies by calculating the Solid Angle Fractions (SAF); the three other candidates include a spherical cap design, a cylindrical design, and the conventional whole body PET. RESULTS: The spherical cap and the dodecahedron have an identical SAF that is 58.4% higher than that of a 30 cm diameter cylinder and 5.44 times higher than that of a 76 cm diameter cylinder. The conceptual polygon-shape detectors (including pentagon and hexagon detectors based on the PMT-light-sharing scheme instead of the conventional square-shaped block detector module) are presented for the polyhedron PET design. Monte Carlo simulations are performed in order to validate the detector decoding. CONCLUSIONS: The results show that crystals in a pentagon-shape detector can be successfully decoded by Anger Logic. The new detector designs support the polyhedron PET investigation.
关键词： polyhedron geometry,Positron emission tomography (PET),brain imaging
更新于2025-09-23 15:22:29
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PET-Liganden für die Diagnostik der Alzheimer-Demenz: Amyloid und Tau
摘要： Over the last 15 years diagnostic imaging of amyloid and tau deposits with PET has gained increasing importance especially in the context of diagnosis of dementia such as Alzheimer's disease. First radiotracers that were developed aimed at the detection of amyloid plaques in the brain. In the meantime the contribution of hyperphosphorylated proteins (TAU) that lead to another type of protein deposits is getting more and more in the focus of current research on the origin of this disease. While a number of 18F-labelled ligands for amyloid imaging have recently been granted marketing authorization and therefore are commercially available and can be used by licensed nuclear medicine physicians throughout Europe and the US, this is not true for radiotracers for TAU-protein imaging. Therefore their use is restricted to clinical trials or to the application of in house manufactured substances. This article should give an overview on characteristics, development and availability of PET tracers for amyloid and tau imaging and in addition to that exemplify the challenges associated with a GMP compliant manufacturing of these short lived radiotracers.
关键词： Alzheimer,18F,Amyloid,11C,PET,Tau
更新于2025-09-23 15:22:29
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Evaluation of [ <sup>11</sup> C]NMS-E973 as a PET tracer for <i>in vivo</i> visualisation of HSP90
摘要： Heat shock protein 90 is an ATP-dependent molecular chaperone important for folding, maturation and clearance of aberrantly expressed proteins and is abundantly expressed (1-2% of all proteins) in the cytosol of all normal cells. In some tumour cells, however, strong expression of HSP90 is also observed on the cell membrane and in the extracellular matrix and the affinity of tumoural HSP90 for ATP domain inhibitors was reported to increase over 100-fold compared to that of HSP90 in normal cells. Here, we explore [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90 and as a potential tool for in vivo quantification of occupancy of HSP90 inhibitors. Methods: HSP90 expression was biochemically characterized in a panel of established cell lines including the melanoma line B16.F10. B16.F10 melanoma xenograft tumour tissue was compared to non-malignant mouse tissue. NMS-E973 was tested in vitro for HSP90 inhibitory activity in several tumour cell lines. HSP90-specific binding of [11C]NMS-E973 was evaluated in B16.F10 melanoma cells and B16.F10 melanoma, prostate cancer LNCaP and PC3, SKOV-3 xenograft tumour slices and in vivo in a B16.F10 melanoma mouse model. Results: Strong intracellular upregulation and abundant membrane localisation of HSP90 was observed in the different tumour cell lines, in the B16.F10 tumour cell line and in B16.F10 xenograft tumours compared to non-malignant tissue. NMS-E973 showed HSP90-specific inhibition and reduced proliferation of cells. [11C]NMS-E973 showed strong binding to B16.F10 melanoma cells, which was inhibited by 200 μM of PU-H71, a non-structurally related HSP90 inhibitor. HSP90-specific binding was observed by in vitro autoradiography of murine B16.F10 melanoma, LNCaP and PC3 prostate cancer and SKOV-3 ovary carcinoma tissue slices. Further, B16.F10 melanoma-inoculated mice were subjected to a μPET study, where the tracer showed fast and persistent tumour uptake. Pretreatment of B16.F10 melanoma mice with PU-H71 or Ganetespib (50 mg/kg) completely blocked tumour accumulation of [11C]NMS-E973 and confirmed in vivo HSP90 binding specificity. HSP90-specific binding of [11C]NMS-E973 was observed in blood, lungs and spleen of tumour-bearing animals but not in control animals. Conclusion: [11C]NMS-E973 is a PET tracer for in vivo visualisation of tumour HSP90 expression and can potentially be used for quantification of HSP90 occupancy. Further translational evaluation of [11C]NMS-E973 is warranted.
关键词： HSP90,melanoma,PET imaging,carbon-11,NMS-E973
更新于2025-09-23 15:22:29
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A Self-Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization
摘要： Translating controlled/living radical polymerization (CLRP) from batch to the high throughput production of polymer libraries presents several challenges in terms of both polymer synthesis and characterization. Although recently there have been significant advances in the field of low volume, high throughput CLRP, techniques able to simultaneously monitor multiple polymerizations in an 'online' manner have not yet been developed. Here, we report our discovery that 5,10,15,20-tetraphenyl-21H,23H-porphine zinc (ZnTPP) is a self-reporting photocatalyst that can mediate PET-RAFT polymerization as well as report on monomer conversion via changes in its fluorescence properties. This enables the use of a microplate reader to conduct high throughput 'online' monitoring of PET-RAFT polymerizations performed directly in 384-well, low volume microtiter plates.
关键词： photochemistry,polymerization,online monitoring,PET-RAFT
更新于2025-09-23 15:22:29
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Synthesis and preclinical evaluation of 68Ga-PSMA-BCH for prostate cancer imaging
摘要： Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. 68Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with 68GaCl3 with >99% radiochemical purity and 59-74 GBq/μmol specific activity. In vitro and in vivo study of 68Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with 68Ga-PSMA-617, 68Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating 68Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.
关键词： 68Ga-PSMA-BCH,PSMA,PET imaging,Prostate cancer
更新于2025-09-23 15:22:29
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Track-etched membrane as fluorescence-based pH biosensor
摘要： Robust and cost-effective stimuli-responsive polymers show prominent advantages to be integrated into detection devices. In addition, modified track-etched membranes with chemical-sensing polymers possess additional robustness features such as including the sensing material into sub-micron pores. In this study, we report the preparation of track-etched PET membranes with fluorescent response in direct relation to changes in the pH of the environment. Immobilised Fluorescein and Green Fluorescent Protein have been used as pH-sensor elements. The former was not sensitive to pH, while the latter had a similar pH sensitivity to that of the free protein. Modifications of track-etched membranes were carried out by grafting polymerisation initiated by the remnant radicals, a straightforward technique for selective modification of the inner wall of pores. The biosensor prepared with the fluorescent protein was able to sense the pH of a buffer solution in the range 4 to 8. Furthermore, this membrane evidenced capacity to sense the pH of the cell growth by in situ fluorescence intensity detection during E.coli cell culture in microwells.
关键词： Track-etched PET membrane,Nanopore functionalisation,GFP immobilisation,Glycidyl methacrylate
更新于2025-09-23 15:22:29