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A small-animal positron emission tomography (PET) scanner using PS-APD (position-sensitive avalanche photodiode) detectors has been developed for simultaneous PET/MRI imaging. In this scanner, up to 16 detector modules (one PS-APD per module) are used, and each detector module produces 4 signals to be digitized with their peak values. This leads to as many as 64 analog outputs to the data acquisition (DAQ) system, requiring 64 DAQ channels. In the future, the system will be extended to 32 modules, resulting in 128 channels. It is possible to sample all channels simultaneously, but most of them do not contain useful data, since only one coincidence event (producing data on 8 channels) is identified each time. The purpose of this work was to develop a general-purpose method for reducing the number of analog inputs to the data acquisition for the sparse fast analog signals produced in a PET scanner. To achieve this, a multiplexer board was designed to sample coincidence events from the PET scanner. The effect of the multiplexer on signal quality was evaluated and the average peak-to-valley ratios in detector flood histograms with and without multiplexer were 2.97 and 3.02 respectively. On-board coincidence, pile-up rejection and multiple coincidence rejection functions were implemented and worked as expected. The dead time performance was also characterized. Index Terms--Avalanche photodiodes, data acquisition, multiplexing, positron emission tomography (PET).

The probability of nodal and distant metastasis in patients (pts) with very-low, low, and favorable intermediate risk (FIR) prostate cancer (PCa) is considered low. Current NCCN and AUA/ASTRO guidelines do not recommend PSMA PET staging for these men. However, it has been reported that pts assigned to the FIR category are more likely than low-risk pts to have adverse pathological findings (upstaging and upgrading) at radical prostatectomy (RP) with a trend toward shorter recurrence-free survival. Early detection of clinically significant disease, extraprostatic extension, seminal vesicle invasion, N1 or M1 disease may change medical management in FIR pts and improve treatment outcomes. The purpose of this study is to explore whether piflufolastat F 18 PET/CT or PET/MR can detect higher risk disease in men previously assessed as FIR by standard of care methods. We hypothesize that piflufolastat F 18 PET will detect non-organ confined disease or upgrade pts to International Society of Urologic Pathologists (ISUP) grade ≥3 PCa in at least 5% of FIR subjects. This trial will also assess the ability for PET to better assess the volume and extent of the intraprostatic cancers. MIRROR is a phase 4, open label single arm multicenter study designed to evaluate the diagnostic performance and safety of piflufolastat F 18 in men with newly diagnosed FIR PCa. Eligible male pts must be ≥18 years of age, no prior PCa treatment, have a life expectancy of at least 13 months as determined by investigator, and confirmed FIR PCa per 2023 NCCN guidelines. The date of the prostate biopsy should be no sooner that 2 weeks and no later than 3 months prior to piflufolastat F 18 PSMA PET imaging. Participants will receive a single dose of piflufolastat F 18 injection followed by a single PET/CT or PET/MRI from mid-thigh through skull vertex acquired at 1 to 2 hours post-injection. Pts with a positive study scan results suspicious for PCa ISUP grade ≥3 or non-organ confined disease may be asked to undergo additional diagnostic test(s) for PCa and/or RP with pelvic lymph node dissection within 2 to 90 days after study scan to determine a truth standard. Pts will be monitored for up to 12 months to collect information about PCa treatment decisions and PSA results. The primary objective is to determine the detection rate defined as the proportion of participants with PCa in whom piflufolastat F 18 PET detected intraprostatic ISUP grade ≥3 lesions as confirmed by pathology, or in whom piflufolastat F 18 PET detected the presence of either/or extraprostatic extension, seminal vesicle invasion, regional lymph node involvement, distant metastases. Additional objectives include: change in intended patient clinical management, correct localization rate, true detection rate, sensitivity, specificity, PPV & NPV against reference standard. The study is currently open in the US. NCT06074510 TBD. TBD. [ABSTRACT FROM AUTHOR]

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores. First-in-human 64 Cu-FBP8 fibrin-targeted positron emission tomography (PET) imaging in seven patients with gastric or gastroesophageal junction cancer showed high probe uptake in all target lesions with tumor-to-background (muscle) uptake ratios of 9.9 ± 6.6 in primary ( n = 7) and 11.2 ± 6.6 in metastatic ( n = 45) tumors. Using two mouse models of human GCa, one fibrin-high (SNU-16) and one fibrin-low (NCI-N87), we showed that PET imaging with a related fibrin-specific peptide, CM500, labeled with copper-64 ( 64 Cu-CM500) specifically bound to and precisely quantified tumor fibrin in both models. We then labeled the fibrin-specific peptide CM600 with yttrium-90 and showed that 90 Y-CM600 effectively decreased tumor growth in these mouse models. Mice carrying fibrin-high SNU-16 tumors experienced tumor growth inhibition and prolonged survival in response to either a single high dosage or fractionated lower dosage of 90 Y-CM600, whereas mice carrying fibrin-low NCI-N87 tumors experienced prolonged survival in response to a fractionated lower dosage of 90 Y-CM600. These results lay the foundation for a fibrin-targeted theranostic that may expand options for patients with advanced GCa.

Purpose: This study presents for the first time in humans the biodistribution, clearance and dosimetry estimates of [ 64 Cu]Fibrin Binding Probe #8 ([ 64 Cu]FBP8) in healthy subjects. [ 64 Cu]FBP8-PET previously demonstrated its potential in two recent applications: thrombus imaging and pulmonary fibrosis., Procedures: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [ 64 Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 h, 4 h and 24 h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software., Results: Subjects were injected with 400 MBq of [ 64 Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [ 64 Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [ 18 F]fluorodeoxyglucose ([ 18 F]FDG, 0.020mSv/MBq)., Conclusions: This study demonstrates the following properties of the [ 64 Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 min in a single session. These properties provide the basis for [ 64 Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions., Competing Interests: Declarations. Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Financial Support and Conflict of Interest: This work was supported by grants from the National Heart Lung and Blood Institute (R01HL109448) and the National Institutes of Health (NIH) Office of the Director (S10OD028499). Peter Caravan holds equity in and receives consulting income from Collagen Medical LLC and Reveal Pharmaceuticals, and has research funding from Transcode Therapeutics, Pliant Therapeutics, and Canon Medical. David Izquierdo-Garcia receives funding from the PolyBio Research Foundation and the Spanish Ministry of Universities., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy. A major challenge in patient management is the lack of a reliable imaging tool to monitor tumor response to treatment. Tumor-associated fibrosis characterized by high type I collagen is a hallmark of PDAC, and fibrosis further increases in response to neoadjuvant chemoradiotherapy (CRT). We hypothesized that molecular positron emission tomography (PET) using a type I collagen-specific imaging probe, 68 Ga-CBP8 can detect and measure changes in tumor fibrosis in response to standard treatment in mouse models and patients with PDAC. Methods: We evaluated the specificity of 68 Ga-CBP8 PET to tumor collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in nude mouse models of human PDAC including FOLFIRNOX-sensitive (PANC-1 and PDAC6) and FOLFIRINOX-resistant (SU.86.86). Next, we demonstrated the specificity and sensitivity of 68 Ga-CBP8 to the deposited collagen in resected human PDAC and pancreas tissues. Eight male participant (49-65 y) with newly diagnosed PDAC underwent dynamic 68 Ga-CBP8 PET/MRI, and five underwent follow up 68 Ga-CBP8 PET/MRI after completing standard CRT. PET parameters were correlated with tumor collagen content and markers of response on histology. Results: 68 Ga-CBP8 showed specific binding to PDAC compared to non-binding 68 Ga-CNBP probe in two mouse models of PDAC using PET imaging and to resected human PDAC using autoradiography (P < 0.05 for all comparisons). 68 Ga-CBP8 PET showed 2-fold higher tumor signal in mouse models following FOLFIRINOX treatment in PANC-1 and PDAC6 models (P < 0.01), but no significant increase after treatment in FOLFIRINOX resistant SU.86.86 model. 68 Ga-CBP8 binding to resected human PDAC was significantly higher (P < 0.0001) in treated versus untreated tissue. PET/MRI of PDAC patients prior to CRT showed significantly higher 68 Ga-CBP8 uptake in tumor compared to pancreas (SUV mean : 2.35 ± 0.36 vs. 1.99 ± 0.25, P = 0.036, n = 8). PET tumor values significantly increased following CRT compared to untreated tumors (SUV mean : 2.83 ± 0.30 vs. 2.25 ± 0.41, P = 0.01, n = 5). Collagen deposition significantly increased in response to CRT (59 ± 9% vs. 30 ± 9%, P=0.0005 in treated vs. untreated tumors). Tumor and pancreas collagen content showed a positive direct correlation with SUV mean (R 2 = 0.54, P = 0.0007). Conclusions: This study demonstrates the specificity of 68 Ga-CBP8 PET to tumor type I collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in PDAC. The results highlight the potential use of collagen PET as a non-invasive tool for monitoring response to treatment in patients with PDAC., Competing Interests: Competing Interests: PC has equity in and is a consultant to Collagen Medical LLC, has equity in Reveal Pharmaceuticals Inc., and has research support from Transcode Therapeutics and Pliant Therapeutics. PC is a co-inventor of US Patent 10,471,162 which covers 68Ga-CBP8 and is assigned to the General Hospital Corporation. SE has research support from Sofie Biosciences, Telix, and Novartis Pharmaceuticals. ARP has held Equity in C2i Genomics, XGenomes, Cadex, Vionix and Parithera. In the last 36 months, she has served as an advisor/consultant for Eli Lilly, Mirati, Pfizer, Inivata, Biofidelity, Checkmate Pharmaceuticals, FMI, Guardant, Abbvie, Bayer, Delcath, Taiho, CVS, Value Analytics Lab, Seagen, Saga, AZ, Scare Inc, Illumina, Taiho, Hookipa, Kahar Medical, Xilio Therapeutics, Sirtex, Takeda, and Science For America. She receives fees from Up to Date. She has received travel fees from Karkinos Healthcare. She has been on the DSMC for a Roche study and on the Steering Committee for Exilixis. She has received research funding to the Institution from PureTech, PMV Pharmaceuticals, Plexxicon, Takeda, BMS, Mirati, Novartis, Erasca, Genentech, Daiichi Sankyo, Syndax, Revolution Medicine and Parthenon. UM is a co-founder, shareholder, and consultant (Scientific Advisory Board) of CytoSite BioPharma. TSH is a consultant for Synthetic Biologics, Novocure, Boston Scientific, Neogenomics, Merck, GSK, NextCure, serves on the advisory board of PanTher Therapeutics (Equity), and Lustgarten Foundation, and has received research funding from Taiho, Astra-Zeneca, BMS, GSK, ItraOp and Ipsen. GMB has sponsored research agreements through her institution with: Olink Proteomics, Teiko Bio, InterVenn Biosciences, Palleon Pharmaceuticals. She served on advisory boards for Iovance, Merck, Nektar Therapeutics, Novartis, and Ankyra Therapeutics. She consults for Merck, InterVenn Biosciences, Iovance, and Ankyra Therapeutics. She holds equity in Ankyra Therapeutics. Other authors declare that they have no competing interests., (© The author(s).)

The Bacillus Calmette-Guérin (BCG) vaccine, which has been used for > 100 years to prevent tuberculosis, is well-established for bladder cancer treatment, and under study for neurological and autoimmune diseases. In patients with type 1 diabetes (T1D), BCG vaccinations have been shown in randomized clinical trials to gradually lower blood sugar to near normal levels. This effect appears to be driven by a BCG-induced shift in lymphoid cells' glucose metabolism from oxidative phosphorylation to aerobic glycolysis. The latter is a state of high glucose utilization that draws more glucose from the blood. Apart from blood, it is unknown whether BCG establishes residence in any organs and alters their glucose metabolism. In this two-year-long clinical trial in type 1 diabetics, we use positron emission tomography (PET) and x-ray computed tomography (CT) to map organs that increase their uptake of the glucose analogue 18 F-fluorodeoxyglucose ( 18 F-FDG) before versus after BCG vaccinations. We also injected BALB/c mice with BCG to test for the presence of BCG in various organs. Results from both studies point to the spleen as the dominant site for glucose uptake and BCG residence. The human spleen is significant because its 47% increase in 18 F-FDG uptake by a large population of lymphocytes and monocytes might help to explain BCG's systemic lowering of blood glucose to near normal levels. Findings suggest that the spleen, triggered by BCG, assumes a critical role in systemic glucose regulation in the absence of a functional pancreas., (© 2024. The Author(s).)

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60-90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study presents the biodistribution, clearance and dosimetry estimates of [ 64 Cu]Fibrin Binding Probe #8 ([ 64 Cu]FBP8) in healthy subjects., Procedures: This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [ 64 Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 hours, 4h and 24h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software., Results: Subjects were injected with ~400 MBq of [ 64 Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [ 64 Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [ 18 F]fluorodeoxyglucose ([ 18 F]FDG, 0.020mSv/MBq)., Conclusions: This study demonstrates the following properties of the [ 64 Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 minutes in a single session. These properties provide the basis for [ 64 Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)-a mitochondrial protein-in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [ 11 C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [ 11 C]PBR28 PET-MRI scans. Females with ASD exhibited elevated [ 11 C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [ 11 C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [ 11 C]PBR28 SUVR across time in both groups. Elevated regional [ 11 C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [ 11 C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD., (© 2024. The Author(s).)

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown. In this proof-of-concept study, we showed, for the first time, the neuroepigenetic biomarker capability of non-invasive imaging of class I histone deacetylase (HDAC) epigenetic enzymes in the in vivo brain for classifying AUD patients from healthy controls using a machine learning approach in the context of precision diagnosis. Eleven AUD patients and 16 age- and sex-matched healthy controls completed a simultaneous positron emission tomography-magnetic resonance (PET/MR) scan with the HDAC-binding radiotracer [ 11 C]Martinostat. Our results showed lower HDAC expression in the anterior cingulate region in AUD. Furthermore, by applying a genetic algorithm feature selection, we identified five particular brain regions whose combined [ 11 C]Martinostat relative standard uptake value (SUVR) features could reliably classify AUD vs. controls. We validate their promising classification reliability using a support vector machine classifier. These findings inform the potential of in vivo HDAC imaging biomarkers coupled with machine learning tools in the objective diagnosis and molecular translation of AUD that could complement the current diagnostic and statistical manual of mental disorders (DSM)-based intervention to propel precision medicine forward., Competing Interests: C.W. and J.M.H. are inventors of the [11C]Martinostat epigenetic PET radiotracer imaging probe used in this project., (© 2024 The Author(s).)

Purpose: Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI., Methods and Materials: Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe 68 Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quantified via autoradiography. 68 Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects., Results: Murine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and 68 Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant 68 Ga-CBP8 uptake in areas of RILI and minimal background uptake., Conclusions: These findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners and inserts are valuable tools for accurate diagnosis, treatment planning, and monitoring due to their complementary information. However, the integration of a PET system into an MRI scanner presents technical challenges for a distortion-free operation., Purpose: We aim to develop a PET insert dedicated to breast imaging in combination with the 3T PET/MRI scanner Biograph mMR (Siemens Healthineers) as well as a brain PET insert for the 7T MRI scanner MAGNETOM Terra (Siemens Healthineers). For this development, we selected as a basis the C13500 series PET modules (Hamamatsu Photonics K.K.) as they offer an all-in-one solution with a scalable, modular design for compact integration with state-of-the-art performance. The original PET modules were not designed to be operated with an MRI scanner, therefore we implemented several modifications such as signal transmission via plastic optical fiber, radio frequency (RF) shielding of the front-end electronics, and filter for the power supply lines. In this work, we evaluated the mutual MRI compatibility between the modified PET modules and the 3T and 7T MRI scanner., Methods: We used a proof-of-concept setup with two detectors to comprehensively evaluate a potential distortion of the performance of the modified PET modules whilst exposing them to a variety of MR sequences up to the peak operation conditions of the Biograph mMR. A method using the periodicity of the sequences to identify distortions of the PET events in the phase of RF pulse transmission was introduced. Vice versa, the potential distortion of the Biograph mMR was evaluated by vendor proprietary MRI compatibility test sequences. Afterwards, these studies were extended to the MAGNETOM Terra., Results: No distortions were introduced by gradient field switching (field strength up to 20 mT/m at a slew rate of 66.0 T/ms -1 ). However, RF pulse transmission induced a reduction of the single event rate from 33.0 kcounts/s to 32.0 kcounts/s and a degradation of the coincidence resolution time from 251 to 299 ps. Further, the proposed method revealed artifacts in the energy and timing histograms. Finally, by using the front-end filters it was possible to prevent any RF pulse induced distortion of event rate, energy, or time stamps even for a 700° flip angle (45.5 μT) sequence. The evaluations to assess potential distortions of the MRI scanner showed that carefully designed RF shielding boxes for the PET modules were required to prevent distortion of the RF spectra. The increase in B 0 field inhomogeneity of 0.254 ppm and local changes of the B 1 field of 12.5% introduced by the PET modules did not qualitatively affect the MR imaging with a spin echo and MPRAGE sequence for the Biograph mMR and the MAGNETOM Terra, respectively., Conclusion: Our study demonstrates the feasibility of using a modified version of the PET modules in combination with 3T and 7T MRI scanners. Building upon the encouraging MRI compatibility results from our proof-of-concept detectors, we will proceed to develop PET inserts for breast and brain imaging using these modules., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche-related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Dedicated brain PET scanners are optimized to provide high sensitivity and high spatial resolution compared with existing whole-body PET systems, and they can be much cheaper to produce and install in various clinical and research settings. Advancements in detector technology over the past few years have placed several standalone PET, PET/computed tomography, and PET/MR systems on or near the commercial market; the features and capabilities of these systems will be reviewed here., (Copyright © 2023 Elsevier Inc. All rights reserved.)