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Preclinical evaluation of a 64Cu-labeled disintegrin for PET imaging of prostate cancer
摘要： A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new 64Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor-bearing mice. Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit and followed by coupling with VCN. The precursor was then radiolabeled with positron emitter 64Cu (t1/2 = 12.7 h) in ammonium acetate buffer to provide 64Cu-Sar-PEG-VCN, which was subsequently subjected to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor-targeting efficacy of 64Cu-Sar-PEG-VCN was compared to a cyclic RGD peptide-based PET probe (64Cu-Sar-RGD). 64Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of > 98%. The specific activity of 64Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that 64Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to 64Cu-Sar-RGD, 64Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66 ± 0.34 vs. 2.88 ± 0.46) and 24 h (4.98 ± 0.80 vs. 3.22 ± 0.30) post-injection (pi) and similar tumor-to-liver ratios at 2 h (0.43 ± 0.09 vs. 0.37 ± 0.04) and 24 h (0.57 ± 0.13 vs. 0.52 ± 0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73 ± 0.36) of 64Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. For both microPET and biodistribution studies at 48 h pi, the PC-3 tumor uptake of 64Cu-Sar-PEG-VCN is lower than that of 64Cu-Sar-RGD. 64Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer.
关键词： Angiogenesis,Disintegrin,PET imaging,Prostate cancer,64Cu,Vicrostatin
更新于2025-09-19 17:13:59
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Nitrone-Modified Gold Nanoparticles: Synthesis, Characterization, and Their Potential as <sup>18</sup> F-Labeled Positron Emission Tomography Probes via I-SPANC
摘要： A novel bioorthogonal gold nanoparticle (AuNP) template displaying interfacial nitrone functional groups for bioorthogonal interfacial strain-promoted alkyne?nitrone cycloaddition reactions has been synthesized. These nitrone?AuNPs were characterized in detail using 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy, and a nanoparticle raw formula was calculated. The ability to control the conjugation of molecules of interest at the molecular level onto the nitrone?AuNP template allowed us to create a novel methodology for the synthesis of AuNP-based radiolabeled probes.
关键词： bioorthogonal chemistry,radiolabeled probes,PET imaging,nitrone,gold nanoparticles
更新于2025-09-12 10:27:22
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Photonuclear production of medical isotopes <sup>62,64</sup> Cu using intense laser-plasma electron source
摘要： 62,64Cu are radioisotopes of medical interest that can be used for positron emission tomography (PET) imaging. Moreover, 64Cu has β? decay characteristics that allow for targeted radiotherapy of cancer. In the present work, a novel approach to experimentally demonstrate the production of 62,64Cu isotopes from photonuclear reactions is proposed in which large-current laser-based electron (e?) beams are generated from the interaction between sub-petawatt laser pulses and near-critical-density plasmas. According to simulations, at a laser intensity of 3.4 × 1021 W/cm2, a dense e? beam with a total charge of 100 nC can be produced, and this in turn produces bremsstrahlung radiation of the order of 1010 photons per laser shot, in the region of the giant dipole resonance. The bremsstrahlung radiation is guided to a natural Cu target, triggering photonuclear reactions to produce the medical isotopes 62,64Cu. An optimal target geometry is employed to maximize the photoneutron yield, and 62,64Cu with appropriate activities of 0.18 GBq and 0.06 GBq are obtained for irradiation times equal to their respective half-lives multiplied by three. The detection of the characteristic energy for the nuclear transitions of 62, 64Cu is also studied. The results of our calculations support the prospect of producing PET isotopes with gigabecquerel-level activity (equivalent to the required patient dose) using upcoming high-intensity laser facilities.
关键词： 62,64Cu,laser-plasma electron source,medical isotopes,Photonuclear production,targeted radiotherapy,PET imaging
更新于2025-09-12 10:27:22
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New 55Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
摘要： Overexpression of folate receptors (FRs) on di?erent tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two 55Co-labeled albumin-binding folate derivatives-[55Co]Co-cm10 and [55Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both 55Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [64Cu]Cu-rf42. Small animal PET/CT images con?rmed the biodistribution results and showed the clear delineation of FR-expressing tumors.
关键词： folate receptors,cobalt-55,PET imaging,albumin binder,ovarian cancer,folic acid
更新于2025-09-12 10:27:22
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18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET imaging of mammary carcinoma
摘要： Neuropeptide Y Y1 receptors (Y1R) have been found to be overexpressed in a number of different tumours, such as breast, ovarian or renal cell cancer. in mammary carcinoma the high Y1R density together with its high incidence of 85% in primary human breast cancers and 100% in breast cancer derived lymph node metastases attracted special attention. therefore, the aim of this study was the development of radioligands for Y1R imaging by positron emission tomography (pet) with a special emphasis on imaging agents with reduced lipophilicity to provide a pet ligand with improved biodistribution in comparison with previously published tracers targeting the Y1R. three new radioligands based on BIBP3226, bearing an 18F-fluoroethoxy linker (12), an 18F-PEG-linker (13) or an 18F-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayed Y1R affinities of 2.8 nM (12), 29 nM (13) and 208 nM (11) and were characterised in vitro regarding binding to human breast cancer MCF-7-Y1 cells and slices of tumour xenografts. In vivo, small animal PET studies were conducted in nude mice bearing MCF-7-Y1 tumours. The binding to tumours, solid tumour slices and tumour cells correlated well with the Y1R affinities. Although 12 and 13 showed displaceable and specific binding to Y1R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios for Y1R imaging by pet. Yet the present study is another step towards an optimized pet radioligand for imaging of Y1R in vivo.
关键词： Neuropeptide Y Y1 receptors,BIBP3226,radioligands,mammary carcinoma,PET imaging
更新于2025-09-11 14:15:04
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Measuring Estrogen Receptor Functionality using Progesterone Receptor PET Imaging: Rising to the (Estradiol) Challenge!
摘要： Prognosis and therapy choice for breast cancer greatly depend upon pathohistological evaluation of biopsies and surgical samples. More specifically, the Estrogen Receptor (ER) – Progesterone Receptor (PR) – human epidermal growth factor receptor 2 (HER2) triad provides crucial information on which clinicians guide their intervention. Indeed, positivity for one or several of those receptors indicates that the use of hormone- or immuno-therapy against their respective targets is likely to benefit the afflicted patient.
关键词： PET Imaging,Breast Cancer,Estradiol Challenge,Progesterone Receptor,Estrogen Receptor
更新于2025-09-10 09:29:36
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PET-Computed Tomography and PET-MR Imaging and Their?Applications in the Twenty-First Century
摘要： Since the discovery of x-ray by Roentgen in 1895, planar radiography has remained a major imaging technique in assessing skeletal abnormalities with reasonable success. However, poor contrast between diseased sites and the background results in low sensitivity of this modality in detecting early disease and monitoring its course over time. The introduction of computed tomography (CT) in 1971 by Hounsfield further enhanced the role of x-ray-based disease assessment, and as such, XCT has played an important role in the day-to-day management of musculoskeletal (MSK) disorders. Since the early 1980s, when the first MR imaging instruments were introduced for human studies, the impact of imaging for examining soft tissue abnormalities in MSK disorders has been substantially enhanced. Currently, XCT and MR imaging are the main imaging modalities available in this domain but suffer from many deficiencies that need to be addressed by employing more advanced approaches. Since the early 1970s, 99m-Technitium (Tc)-labeled phosphates have been extensively used to detect benign and malignant disorders of the skeletal system. These radiotracers allow planar and tomographic imaging (SPECT [single-photon emission computed tomography]), but the quality of images generated is somewhat suboptimal for detection of the affected sites and quantification of the disease activity.
关键词： PET-CT-MRI,musculoskeletal disorders,radiotracers,FDG-PET,imaging,18F-NaF
更新于2025-09-09 09:28:46
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Development of 2-(2-(3-(4-([18F]Fluoromethoxy-d2)phenyl)-7-methyl- 4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron Emission Tomography Imaging of Phosphodiesterase 10A (PDE10A) in Brain
摘要： Phosphodiesterase 10A (PDE10A) is a newly identified therapeutic target for central nervous system disorders. 2-(2-(3-(4-([18F]Fluoroethoxy)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659, [18F]5) is a useful positron emission tomography (PET) ligand for imaging of PDE10A in the human brain. However, the radiolabeled metabolite of [18F]5 can accumulate in the brain. In this study, using [18F]5 as a lead compound, we designed four new 18F-labeled ligands ([18F]6–9) to find one more suitable than [18F]5. Of these, 2-(2-(3-(4-([18F]fluoromethoxy-d2)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]9) exhibited high in vitro binding affinity (Ki = 2.9 nM) to PDE10A and suitable lipophilicity (LogD = 2.2). In PET studies, the binding potential (BPND) of [18F]9 (5.8) to PDE10A in rat brains was significantly higher than that of [18F]5 (4.6). Furthermore, metabolite analysis showed much lower levels of contamination with radiolabeled metabolites of [18F]9 in the brain than those of [18F]5. In conclusion, [18F]9 is a useful PET ligand for PDE10A imaging in brain.
关键词： [18F]MNI-659,PDE10A,PET imaging,[18F]fluoromethoxy-d2,brain,Phosphodiesterase 10A,radioligand
更新于2025-09-09 09:28:46
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Prototype time-of-flight PET utilizing capacitive multiplexing readout method
摘要： Positron emission tomography (PET) is an imaging technique that provides the spatial distribution of radiopharmaceuticals labeled with positron emitting radioisotopes by detecting the gamma rays produced from positron-electron annihilation. Recently, a time-of-flight (TOF) PET has drawn an increasing attention because it is capable of reducing the scan time or injected dose with improved the signal-to-noise ratio (SNR) in reconstructed PET images by precisely localizing the emission point along the line-of-response using TOF information. This study presents a multiplexing method that can effectively reduce the number of readout channels of a silicon photomultiplier (SiPM) based TOF PET while achieving excellent timing resolution. A capacitive multiplexing method was employed that could improve the degradation of the timing performance occurring in a conventional resistive multiplexing method. In addition, a high-speed signal processing method is also presented for the TOF PET. A TOF PET prototype was developed to demonstrate the imaging capability of the TOF PET system. A flood histogram of a PET detector module, composed of an 8×8 array of 3.01×3.01×20.00 mm3 lutetium fine silicate (LFS) scintillators and an 8×8 array of 3.16×3.16 mm2 SiPMs, was acquired using the proposed method. All 64 scintillators were successfully resolved in the flood histogram. The average energy resolution and coincidence resolving time (CRT) were 14.2±1.1% and 431±41 ps full width at half maximum (FWHM), respectively. A tomographic image of the hot-rod phantom was successfully acquired using the TOF PET prototype, and rods with a size of 2.4 mm in diameter were clearly resolved in the reconstructed image.
关键词： PET imaging,silicon photomultiplier,Time-of-flight PET,capacitive multiplexing,timing resolution
更新于2025-09-04 15:30:14
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Dose reconstruction from PET images in carbon ion therapy: a deconvolution approach
摘要： Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the β+-decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively.
关键词： evolutionary algorithm,PET imaging,range verification,carbon ion therapy,dose reconstruction
更新于2025-09-04 15:30:14