PET Applications Research Articles

Tuning the Properties of Rigidified Acyclic DEDPA2- Derivatives for Application in PET Using Copper-64.

We present a detailed investigation of the coordination chemistry toward [natCu/64Cu]copper of a series of H2DEDPA derivatives (H2DEDPA = 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (H2CHXDEDPA), cyclopentyl (H2CpDEDPA) or cyclobutyl (H2CBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a H2CBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl ring, which can be used for conjugation to targeting units. The X-ray structures of the Cu(II) complexes evidence distorted octahedral coordination around the metal ion in all cases. Cyclic voltammetry experiments (0.15 M NaCl) evidence quasi-reversible reduction waves associated with the reduction of Cu(II) to Cu(I). The complexes show a high thermodynamic stability, with log KCuL values of 25.11(1), 22.18(1) and 20.19(1) for the complexes of CHXDEDPA2-, CpDEDPA2- and CBuDEDPA2-, respectively (25 °C, 1 M NaCl). Dissociation kinetics experiments reveal that both the spontaneous- and proton-assisted pathways operate at physiological pH. Quantitative labeling with 64CuCl2 was observed at 0.1 nmol for CHXDEDPA2- and CpDEDPA2-, 0.025 nmol for CBuDEDPA2- and 1 nmol for CBuDEDPA-NHBoc2-, with no significant differences observed at 15, 30, and 60 min. The radio-complexes are stable in PBS over a period of 24 h.

Recent Updates of PET in Lymphoma: FDG and Beyond

Lymphoma is one of the most common cancers worldwide, categorized into Hodgkin lymphoma and non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has become an essential imaging tool for evaluating patients with lymphoma in terms of initial diagnosis, staging, prognosis, and treatment response assessment. Recent advancements in imaging technology and methodologies, along with the development of artificial intelligence, have revolutionized the evaluation of complex imaging data, enhancing the diagnostic and predictive power of PET in lymphoma. However, FDG is not cancer-specific, but it primarily reflects glucose metabolism, which has prompted the investigation of alternative PET tracers to address this limitation. Novel PET radiotracers, such as fibroblast activation protein inhibitors targeting the tumor microenvironment, have recently shown promising results in evaluating various malignancies compared to FDG PET. Furthermore, with the rapid advancements in immunotherapy and the favorable imaging properties of 89Zr, immunoPET has emerged as a promising modality, offering insights into the functional and molecular status of the immune system. ImmunoPET can also facilitate the development of new antibody therapeutics and radioimmunotherapy by providing pharmacokinetic and pharmacodynamic data. This review provides comprehensive insights into the current clinical applications of FDG PET in lymphoma, while also exploring novel PET imaging radiotracers beyond FDG, discussing their mechanisms of action and potential impact on patient management.

Positronium lifetime validation measurements using a long-axial field-of-view positron emission tomography scanner

BackgroundPositron emission tomography (PET) traditionally uses coincident annihilation photons emitted from a positron interacting with an electron to localize cancer within the body. The formation of positronium (Ps), a bonded electron-positron pair, has not been utilized in clinical applications of PET due to the need to detect either the emission of a prompt gamma ray or the decay of higher-order coincident events. Assessment of the lifetime of the formed Ps, however, can potentially yield additional diagnostic information of the surrounding tissue because Ps properties vary due to void size and molecular composition. To assess the feasibility of measuring Ps lifetimes with a PET scanner, experiments were performed in a Biograph Vision Quadra (Siemens Healthineers). Quadra is a long-axial field-of-view (LA-FOV) PET scanner capable of producing list-mode data from single interaction events.ResultsOrtho-Ps (o-Ps) lifetimes were measured for quartz-glass and polycarbonate samples using a 22Na\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{22}\ ext{Na}$$\\end{document} positron source. Results produced o-Ps lifetimes of 1.538 ± 0.036 ns for the quartz glass and 1.927 ± 0.042 ns for the polycarbonate. Both o-Ps lifetimes were determined using a double-exponential fit to the time-difference distribution between the emission of a prompt gamma ray and the annihilation of the correlated positron. The measured values match within a single standard deviation of previously published results. The quartz-glass samples were additional measured with 82Rb\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${^{82}}\ ext{Rb}$$\\end{document}, 68\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{68}$$\\end{document}Ga and 124I\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{124}\ ext{I}$$\\end{document} to validate the lifetime using clinically available sources. A double-exponential fit was initially chosen as a similar methodology to previously published works, however, an exponentially-modified Gaussian distribution fit to each lifetime more-accurately models the data. A Bayesian method was used to estimate the variables of the fit and o-Ps lifetime results are reported using this methodology for the three clinical isotopes: 1.59 ± 0.03 ns for 82Rb\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{82}\ ext{Rb}$$\\end{document}, 1.58 ± 0.07 ns for 68Ga\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{68}\ ext{Ga}$$\\end{document} and 1.62 ± 0.01 ns for 124I\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{124}\ ext{I}$$\\end{document}. The impact of scatter and attenuation on the o-Ps lifetime was also assessed by analyzing a water-filled uniform cylinder (20 ϕ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\phi$$\\end{document}×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} 30 cm3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{3}$$\\end{document}) with an added 82Rb\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{82}\ ext{Rb}$$\\end{document} solution. Lifetimes were extracted for various regions of the cylinder and while there is a shape difference in the lifetime due to scatter, the extracted o-Ps lifetime of the water, 1.815 ± 0.013 ns, agrees with previously published results.ConclusionOverall, the methodology presented in this manuscript demonstrates the repeatability of Ps lifetime measurements with clinically available isotopes in a commercially-available LA-FOV PET scanner. This validation work lays the foundation for future in-vivo patient scans with Quadra.

Application of SV2A PET in neurodegenerative disorders

Application of SV2A PET in neurodegenerative disorders

Current Applications of PET/MR: Part I: Technical Basics and Preclinical/Clinical Applications.

Positron emission tomography/magnetic resonance (PET/MR) imaging has gone through major hardware improvements in recent years, making it a reliable state-of-the-art hybrid modality in clinical practice. At the same time, image reconstruction, attenuation correction, and motion correction algorithms have significantly evolved to provide high-quality images. Part I of the current review discusses technical basics, pre-clinical applications, and clinical applications of PET/MR in radiation oncology and head and neck imaging. PET/MR offers a broad range of advantages in preclinical and clinical imaging. In the preclinic, small and large animal-dedicated devices were developed, making PET/MR capable of delivering new insight into animal models in diseases and facilitating the development of methods that inform clinical PET/MR. Regarding PET/MR's clinical applications in radiation medicine, PET and MR already play crucial roles in the radiotherapy process. Their combination is particularly significant as it can provide molecular and morphological characteristics that are not achievable with other modalities. In addition, the integration of PET/MR information for therapy planning with linear accelerators is expected to provide potentially unique biomarkers for treatment guidance. Furthermore, in clinical applications in the head and neck region, it has been shown that PET/MR can be an accurate modality in head and neck malignancies for staging and resectability assessment. Also, it can play a crucial role in diagnosing residual or recurrent diseases, reliably distinguishing from oedema and fibrosis. PET/MR can furthermore help with tumour characterization and patient prognostication. Lastly, in head and neck carcinoma of unknown origin, PET/MR, with its diagnostic potential, may obviate multiple imaging sessions in the near future.

New full-counts phase-matched data-driven gated (DDG) PET/CT.

Data-driven gated (DDG) PET has gained clinical acceptance and has been shown to match or outperform external-device gated (EDG) PET. However, in most clinical applications, DDG PET is matched with helical CT acquired in free breathing (FB) at a random respiratory phase, leaving registration, and optimal attenuation correction (AC) to chance. Furthermore, DDG PET requires additional scan time to reduce image noise as it only preserves 35%-50% of the PET data at or near the end-expiratory phase of the breathing cycle. A new full-counts, phase-matched (FCPM) DDG PET/CT was developed based on a low-dose cine CT to improve registration between DDG PET and DDG CT, to reduce image noise, and to avoid increasing acquisition times in DDG PET. A new DDG CT was developed for three respiratory phases of CT images from a low dose cine CT acquisition of 1.35mSv for a coverage of about 15.4cm: end-inspiration (EI), average (AVG), and end-expiration (EE) to match with the three corresponding phases of DDG PET data: -10% to 15%; 15% to 30%, and 80% to 90%; and 30% to 80%, respectively. The EI and EE phases of DDG CT were selected based on the physiological changes in lung density and body outlines reflected in the dynamic cine CT images. The AVG phase was derived from averaging of all phases of the cine CT images. The cine CT was acquired over the lower lungs and/or upper abdomen for correction of misregistration between PET and FB CT as well as DDG PET and FB CT. The three phases of DDG CT were used for AC of the corresponding phases of PET. After phase-matched AC of each PET dataset, the EI and AVG PET data were registered to the EE PET data with deformable image registration. The final result was FCPM DDG PET/CT which accounts for all PET data registered at the EE phase. We applied this approach to 14 18F-FDG lung cancer patient studies acquired at 2min/bed position on the GE Discovery MI (25-cm axial FOV) and evaluated its efficacy in improved quantification and noise reduction. Relative to static PET/CT, the SUVmax increases for the EI, AVG, EE, and FCPM DDG PET/CT were 1.67±0.40, 1.50±0.28, 1.64±0.36, and 1.49±0.28, respectively. There were 10.8% and 9.1% average decreases in SUVmax from EI and EE to FCPM DDG PET/CT, respectively. EI, AVG, and EE DDG PET/CT all maintained increased image noise relative to static PET/CT. However, the noise levels of FCPM and static PET were statistically equivalent, suggesting the inclusion of all counts was able to decrease the image noise relative to EI and EE DDG PET/CT. A new FCPM DDG PET/CT has been developed to account for 100% of collected PET data in DDG PET applications. Image noise in FCPM is comparable to static PET, while small decreases in SUVmax were also observed in FCPM when compared to either EI or EE DDG PET/CT.

Dynamic Human Brain Imaging with a Portable PET Camera: Comparison to a Standard Scanner.

Portable, cost-effective PET cameras can radically expand the applicability of PET. We present here a within-participant comparison of fully quantified [18F]FDG dynamic scans in healthy volunteers using the standard Biograph mCT scanner and portable CerePET scanner. Methods: Each of 20 healthy volunteers underwent dynamic [18F]FDG imaging with both scanners (1-154 d apart) and concurrent arterial blood sampling. Tracer SUV, net influx rate (Ki), and the corresponding cerebral metabolic rate of glucose (CMRglu) were quantified at regional and voxel levels. Results: At the regional level, CerePET outcome measure estimates within participants robustly correlated with Biograph mCT estimates in the neocortex, wherein the average Pearson correlation coefficients across participants ± SD were 0.83 ± 0.07 (SUV) and 0.85 ± 0.08 (Ki and CMRglu). There was also strong agreement between CerePET and Biograph mCT estimates, wherein the average regression slopes across participants were 0.84 ± 0.17 (SUV), 0.83 ± 0.17 (Ki), and 0.85 ± 0.18 (CMRglu). There was similar bias across participants but higher correlation and less variability in subcortical regions than in cortical regions. Pearson correlation coefficients for subcortical regions equaled 0.97 ± 0.02 (SUV) and 0.97 ± 0.03 (Ki and CMRglu), and average regression slopes equaled 0.79 ± 0.14 (SUV), 0.83 ± 0.11 (Ki), and 0.86 ± 0.11 (CMRglu). In voxelwise assessment, CerePET and Biograph mCT estimates across outcome measures were significantly different only in a cluster of left frontal white matter. Conclusion: Our results indicate robust correlation and agreement between semi- and fully quantitative brain glucose metabolism measurements from portable CerePET and standard Biograph mCT scanners. The results obtained with a portable PET scanner in this comparison in humans require follow-up but lend confidence to the feasibility of more flexible and portable brain imaging with PET.

P-236 - Site-specific 89Zr-labeling of a VHH construct as a half-life extending building block for PET and TRNT applications

P-236 - Site-specific 89Zr-labeling of a VHH construct as a half-life extending building block for PET and TRNT applications

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology.

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

Comparisons of 3D printed materials for biomedical imaging applications

ABSTRACT In biomedical imaging, it is desirable that custom-made accessories for restraint, anesthesia, and monitoring can be easily cleaned and not interfere with the imaging quality or analyses. With the rise of 3D printing as a form of rapid prototyping or manufacturing for imaging tools and accessories, it is important to understand which printable materials are durable and not likely to interfere with imaging applications. Here, 15 3D printable materials were evaluated for radiodensity, optical properties, simulated wear, and capacity for repeated cleaning and disinfection. Materials that were durable, easily cleaned, and not expected to interfere with CT, PET, or optical imaging applications were identified.

Investigation of the quarter-dose 18 F-FDG total-body PET in routine clinical practice and its clinical value.

The purpose of the study was to evaluate the routine clinical application of total-body PET with quarter-dose 18 F-FDG. The contrast recovery coefficient (CRC) and coefficient of variation (COV) were evaluated among full-, half-, and quarter-dose groups with an acquisition duration of 10-, 5-, 3-, and 1-min in the NEMA (IQ) phantom test. Fifty patients undergoing total-body PET/CT with quarter-dose (0.925MBq/kg) of 18 F-FDG were included in the prospective study. The acquisition time was 10 min, divided into duration groups of 5-, 3-, and 1-min, referred to as G10, G5, G3, and G1. Visual scores were assessed based on overall visual assessment, noise scoring, and lesion conspicuity. Lesion SUV max and TBR were evaluated in semi-quantitative analysis. G10 was used as the gold reference to evaluate lesion detectability. In the phantom study, the COV value of the images with quarter-dose 18 F-FDG and 10-min acquisition time was 11.52%. For spheres with 10 mm diameter, the CRC of quarter-dose PET images was relatively stable compared to that of full-dose groups with all acquisition durations. In the human study, the visual score in G10, G5, and G3 was significantly higher than that in G1. The differences in lesion SUV max and TBR for G1-G10 were significantly higher than that for G5-G10 and G3-G10. All lesions in G10 could be identified in G5 and G3. The phantom and human findings demonstrated the feasibility of quarter-dose 18 F-FDG PET with 3-min acquisition time, which can maintain image quality with reduced radiation dose.

FedFTN: Personalized federated learning with deep feature transformation network for multi-institutional low-count PET denoising

Low-count PET is an efficient way to reduce radiation exposure and acquisition time, but the reconstructed images often suffer from low signal-to-noise ratio (SNR), thus affecting diagnosis and other downstream tasks. Recent advances in deep learning have shown great potential in improving low-count PET image quality, but acquiring a large, centralized, and diverse dataset from multiple institutions for training a robust model is difficult due to privacy and security concerns of patient data. Moreover, low-count PET data at different institutions may have different data distribution, thus requiring personalized models. While previous federated learning (FL) algorithms enable multi-institution collaborative training without the need of aggregating local data, addressing the large domain shift in the application of multi-institutional low-count PET denoising remains a challenge and is still highly under-explored. In this work, we propose FedFTN, a personalized federated learning strategy that addresses these challenges. FedFTN uses a local deep feature transformation network (FTN) to modulate the feature outputs of a globally shared denoising network, enabling personalized low-count PET denoising for each institution. During the federated learning process, only the denoising network’s weights are communicated and aggregated, while the FTN remains at the local institutions for feature transformation. We evaluated our method using a large-scale dataset of multi-institutional low-count PET imaging data from three medical centers located across three continents, and showed that FedFTN provides high-quality low-count PET images, outperforming previous baseline FL reconstruction methods across all low-count levels at all three institutions.

Low-dose TOF-PET based on surface electron production in dielectric laminar MCPs

We present simulations of whole-body low-dose time-of-flight positron emission tomography (TOF-PET) based on the direct surface production (Domurat-Sousa et al., 2023) by 511 keV gamma rays of energetic electrons via the Photo-electric and Compton Effects, eliminating the scintillator and photodetector sub-systems in PET scanners. In Ref. Domurat-Sousa et al. (2023) we described Microchannel Plates (MCP) constructed from thin dielectric laminae containing heavy nuclei such as lead or tungsten (LMCPTM). The laminae surfaces are micro-patterned to form channels, which can then be functionalized to support secondary electron emission in the manner of conventional MCPs. After assembly of the laminae, the channels form the pores of the conversion LMCP. This conversion stage is then followed by a high-gain MCP-based amplification stage, which also can be constructed using the laminar technique, but with pores typical of currently-available large-area MCPs .We have simulated direct conversion using modifications to the TOPAS Geant4-based tool kit. A 20 × 20 × 2.54 cm3 LMCP, composed of 150-micron thick lead-glass laminae, is predicted to have a ≥30% conversion efficiency to a primary electron that penetrates an interior wall of a pore. The subsequent secondary electron shower is largely confined to one pore and can provide high space and time resolutions.In whole-body PET scanners the technique eliminates the scintillator and photodetector subsystems. The consequent absence of a photocathode allows assembly of large arrays at atmospheric pressure and less stringent vacuum requirements, including use of pumped and cycled systems.TOPAS simulations of the Derenzo and XCAT-brain phantoms are presented with dose reductions of factors of 100 and 1000 from a literature benchmark. New applications of PET at a significantly lower radiation dose include routine screening for early detection of pathologies, the use in diagnostics in previously unserved patient populations such as children, and a larger installed facility base in rural and under-served populations, where simpler gamma detectors and lower radiation doses may enable small low-cost portable PET scanners.

Evaluation of a semi-automated approach for FDG PET image analysis for routine clinical application in patients with multiple myeloma

BackgroundFDG PET/CT is a tool for assessing response to therapy in various cancers, and may provide an earlier biomarker of clinical response. We developed a novel semi-automated approach for analyzing FDG PET/CT images in patients with multiple myeloma (MM) to standardize FDG PET application. MethodsPatients (n = 8) with relapsed/refractory MM from the Phase 2 study (NCT02899052) of venetoclax plus carfilzomib and dexamethasone underwent FDG PET/CT at baseline and up to two timepoints during treatment. Images were processed using an established automated segmentation algorithm, with the modification that a red marrow region in an unaffected lumbar vertebra was used to define background standardized uptake value normalized to lean body mass (SUL) threshold above which uptake was considered disease-specific uptake. This approach was compared to lesion segmentation, and to International Myeloma Working Group (IMWG) response criteria, including minimal residual disease (MRD). ResultsThe two FDG PET analysis techniques agreed on evaluation of patient-level SULpeak for 67% of scans. In the metabolic response assessment per PET Response Criteria in Solid Tumors (PERCIST), the two techniques agreed in 75% of patients. Differences between techniques occurred in low-uptake lesions due to greater reader sensitivity to lesions with uptake marginally above background. PERCIST outcomes were generally in agreement with IMWC and MRD. ConclusionsThis semi-automated analysis was in high agreement with standard approaches for detecting response to MM therapy. This proof-of-concept study suggests that larger studies should be conducted to confirm how FDG PET analysis may aid early response detection in MM.

Novel PET Applications and Radiotracers for Imaging Cardiovascular Pathophysiology

PET allows the assessment of cardiovascular pathophysiology across a wide range of cardiovascular conditions. By imaging processes directly involved in disease progression and adverse events, such as inflammation and developing calcifications (microcalcifications), PET can not only enhance our understanding of cardiovascular disease, but also, as shown for 18F-sodium fluoride, has the potential to predict hard endpoints. In this review, the recent advances in disease activity assessment with cardiovascular PET, which provide hope that this promising technology could be leveraged in the clinical setting, shall be discussed.

First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma.

Nectin-4 is an emerging biomarker for cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first nectin-4 targeting antibody-drug conjugate for treating advanced urothelial carcinoma (UC). A PET imaging method to noninvasively quantify nectin-4 expression level would potentially help to select patients most likely to respond to EV and predict the response. In this study, we designed a bicyclic peptide-based nectin-4 targeting radiotracer 68Ga-N188. Initially, we performed preclinical evaluations of 68Ga-N188 in UC cell lines and xenograft mouse models. Next, we performed the translational study in healthy volunteers and a pilot cohort of patients with advanced UC on uEXPLORER total-body PET/CT. In the preclinical study, 68Ga-N188 showed high affinity to nectin-4, specific uptake in a nectin-4(+) xenograft mouse model, and suitable pharmacokinetic and safety profiles. In the translational study, 2 healthy volunteers and 14 patients with advanced UC were enrolled. The pharmacokinetic profile was determined for 68Ga-N188, and the nectin-4 relative expression level in different organs was quantitatively imaged. A clear correlation between PET SUV value and nectin-4 expression was observed, supporting the application of 68Ga-N188 PET as a companion diagnostic tool for optimizing treatments that target nectin-4. See related commentary by Jiang et al., p. 3259.

Role of Exendin-4 Functional Imaging in Diagnosis of Insulinoma: A Systematic Review.

Insulinomas are the most common neuroendocrine neoplasms of the pancreas. Diagnosis is made through patient clinical presentation with hypoglycemia symptoms and imaging, such as EUS, CT, MRI, and functional imaging. Exendin-4 PET/CT (and SPECT/CT) is a new prominent radiotracer developed to image insulinomas. The aim of the study is to evaluate whether exendin-4 imaging is a useful tool in imaging for insulinoma patients when other imaging methods do not reach them. MEDLINE research conducted on PubMed, Scopus, and Web of Science gathered a total of 501 papers. Studies that evaluated exendin-4 SPECT and PET in insulinoma patients were screened and assessed through QUADAS-2 for risk of bias and applicability concerns' assessment. Sensitivity, specificity, and accuracy were reported when available. A total of 13 studies were deemed eligible for a QUADAS 2 review. Studies included ranged from 2009 to 2022. The most-used tracer was 68Ga-DOTA-exendin-4 in PET and 111In-DTPA-exendin-4 in SPECT. Exendin-4 labeled with 99mTc was also reported. The QUADAS-2 risk of bias assessment was overall low, with some unclear reports in the reference and index domains. Only two domains were at high risk of bias because of an explicated non-blind imaging review. Applicability concerns for bias were low in all domains. Reported sensitivities ranged from 95% to 100% and specificities from 20% to 100%. exendin-4 imaging is a sensitive functional imaging tracer in both SPECT and PET applications, especially in suspicion of benign insulinomas located where endoscopic ultrasound cannot reach, being more sensitive than morfostructural imaging.

Assessment of 18F-DCFPyL PSMA PET/CT and PET/MR quantitative parameters for reference standard organs: Inter-reader, inter-modality, and inter-patient variability.

Prostate specific membrane antigen (PSMA)-based radiotracers have shown promise for prostate cancer assessment. Evaluation of quantitative variability and establishment of reference standards are important for optimal clinical and research utility. This work evaluates the variability of PSMA-based [18F]DCFPyL (PyL) PET quantitative reference standards. Consecutive eligible patients with biochemically recurrent prostate cancer were recruited for study participation from August 2016-October 2017. After PyL tracer injection, whole body PET/CT (wbPET/CT) was obtained with subsequent whole body PET/MR (wbPET/MR). Two readers independently created regions of interest (ROIs) including a 40% standardized uptake value (SUV) threshold ROI of the whole right parotid gland and separate spherical ROIs in the superior, mid, and inferior gland. Additional liver (right lobe) and blood pool spherical ROIs were defined. Bland-Altman analysis, including limits of agreement (LOA), as well as interquartile range (IQR) and coefficient of variance (CoV) was used. Twelve patients with prostate cancer were recruited (mean age, 61.8 yrs; range 54-72 years). One patient did not have wbPET/MR and was excluded. There was minimal inter-reader SUVmean variability (bias±LOA) for blood pool (-0.13±0.42; 0.01±0.41), liver (-0.55±0.82; -0.22±1.3), or whole parotid gland (-0.05±0.31; 0.08±0.24) for wbPET/CT and wbPET/MR, respectively. Greater inter-reader variability for the 1-cm parotid gland ROIs was present, for both wbPET/CT and wbPET/MR. Comparing wbPET/CT to the subsequently acquired wbPET/MR, blood pool had a slight decrease in SUVmean. The liver as well as parotid gland showed a slight increase in activity although the absolute bias only ranged from 0.45-1.28. The magnitude of inter-subject variability was higher for the parotid gland regardless of modality or reader. In conclusion, liver, blood pool, and whole parotid gland quantitation show promise as reliable reference normal organs for clinical/research PET applications. Variability with 1-cm parotid ROIs may limit its use.

Emerging and Evolving Concepts in Cancer Immunotherapy Imaging.

Criteria based on measurements of lesion diameter at CT have guided treatment with historical therapies due to the strong association between tumor size and survival. Clinical experience with immune checkpoint modulators shows that editing immune system function can be effective in various solid tumors. Equally, novel immune-related phenomena accompany this novel therapeutic paradigm. These effects of immunotherapy challenge the association of tumor size with response or progression and include risks and adverse events that present new demands for imaging to guide treatment decisions. Emerging and evolving approaches to immunotherapy highlight further key issues for imaging evaluation, such as dissociated response following local administration of immune checkpoint modulators, pseudoprogression due to immune infiltration in the tumor environment, and premature death due to hyperprogression. Research that may offer tools for radiologists to meet these challenges is reviewed. Different modalities are discussed, including immuno-PET, as well as new applications of CT, MRI, and fluorodeoxyglucose PET, such as radiomics and imaging of hematopoietic tissues or anthropometric characteristics. Multilevel integration of imaging and other biomarkers may improve clinical guidance for immunotherapies and provide theranostic opportunities.

Transparent and flame-retardant hybrid protective coating with high surface hardness, yet foldability

With the rapid development of flexible OLED display technology, Poly(ethylene terephthalate) (PET) has also received extensive attention as a protective film. However, it is still a challenge to endow PET with abrasion resistance and flame retardancy while maintaining transparency and flexibility. Here, we developed an epoxy-amine curing hybrid coating based on phosphorus-containing organic amine (DPNP) and ladderlike epoxy-oligosiloxane (AEOS). The ratio of DPNP and AEOS was changed to study the effect of phosphorus and silicon content on the performance of hybrid coatings. All the coatings were transparent. The PET/AE-DP3 sample achieved the limiting oxygen index of 28 % and exhibited self-extinguishing in vertical burning test. In microscale combustion calorimeter (MCC) test, the minimum peak heat release rate was 236.4 W/g with a reduction of 29.5 %, compared with pure PET. In addition, the AE-DP3 coating could withstand the abrasion of copper mesh and cheese cotton with a pencil hardness of 8H, and showed good foldability with a bending diameter of 5 mm. At the same time, the coating exhibited satisfactory adhesion without plasma treatment and good UV resistance. These results indicated the hybrid coating overcome the inherited weakness of PET film such as poor scratch-resistance and flammability, promoting the wider application of PET.