-
Quantitative Total-Body Imaging of Blood Flow with High-Temporal-Resolution Early Dynamic 18F-FDG PET Kinetic Modeling J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Kevin J. Chung, Abhijit J. Chaudhari, Lorenzo Nardo, Terry Jones, Moon S. Chen, Ramsey D. Badawi, Simon R. Cherry, Guobao WangPast efforts to measure blood flow with the widely available radiotracer 18F-FDG were limited to tissues with high 18F-FDG extraction fraction. In this study, we developed an early dynamic 18F-FDG PET method with high-temporal-resolution (HTR) kinetic modeling to assess total-body blood flow based on deriving the vascular phase of 18F-FDG transit and conducted a pilot comparison study against a 11C-butanol
-
Feasibility of an Ultra-Low-Dose PET Scan Protocol with CT-Based and LSO-TX–Based Attenuation Correction Using a Long–Axial-Field-of-View PET/CT Scanner J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Hasan Sari, Mohammadreza Teimoorisichani, Marco Viscione, Clemens Mingels, Robert Seifert, Kuangyu Shi, Michael Morris, Eliot Siegel, Babak Saboury, Thomas Pyka, Axel RomingerLong–axial-field-of-view (LAFOV) PET scanners enable substantial reduction in injected radiotracer activity while maintaining clinically feasible scan times. Whole-body CT scans performed for PET attenuation correction can significantly add to total radiation exposure. We investigated the feasibility of an ultra-low-dose PET protocol and the application of a CT-less PET attenuation correction method
-
Feasibility of Ultra-Low-Activity 18F-FDG PET/CT Imaging Using a Long–Axial-Field-of-View PET/CT System J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Charlotte L.C. Smith, Gerben J. C. Zwezerijnen, Marijke E. den Hollander, Josée M. Zijlstra, C. Willemien Menke-van der Houven van Oordt, Idris Bahce, Maqsood Yaqub, Ronald Boellaard18F-FDG PET/CT imaging is widely used in oncology. Long–axial-field-of-view (LAFOV) PET/CT systems exhibit ultrahigh sensitivity and signal-to-noise ratios, enabling significant reductions in tracer activity and shorter acquisition times. This study aimed to evaluate the feasibility of using ultralow activities for semiquantitative measurements in 18F-FDG PET/CT imaging performed on an LAFOV PET/CT
-
Is Long–Axial-Field-of-View PET/CT Cost-Effective? An International Health–Economic Analysis J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Ian Alberts, Stuart More, Karen Knapp, Riccardo Mei, Stefano Fanti, Clemens Mingels, Lorenzo Nardo, Nii Boye Hammond, Harish Nagaraj, Axel Rominger, Gary J.R. Cook, Don WilsonOur aim is to assess the cost-effectiveness of long–axial-field-of-view (LAFOV) versus short–axial FOV (SAFOV) PET/CT systems using international data. Methods: Our model compares equipment and operational costs for a PET/CT center and investigates the effect of camera choice (SAFOV vs. LAFOV) and operational models. Variables include scanner, personnel, radiopharmaceuticals, and operational costs
-
An External, Independent Validation of an O-(2-[18F]Fluoroethyl)-l-Tyrosine PET Automatic Segmentation Network on a Single-Center, Prospective Dataset of Patients with Glioblastoma J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Nathaniel Barry, Jake Kendrick, Pejman Rowshanfarzad, Ghulam Mubashar Hassan, Roslyn J. Francis, Nicholas Bucknell, Eng-Siew Koh, Andrew M. Scott, Martin A. Ebert, Robin Gutsche, Keith George Ciantar, Norbert Galldiks, Karl-Josef Langen, Philipp LohmannThe goal of this study was to conduct an external, independent validation of an O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET automatic segmentation network on a cohort of patients with glioblastoma. Methods: Twenty-four patients with glioblastoma were included in this study who underwent a total of 52 [18F]FET PET scans (preradiotherapy, n = 23; preradiotherapy retest, n = 9; follow-up, n = 20)
-
In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [11C]HSP990 in Healthy Aging and Neurodegeneration J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Romy Cools, Koen Vermeulen, Eline Vonck, Veerle Baekelandt, Cassis Varlow, Valeria Narykina, Christopher Cawthorne, Koen Van Laere, Wim Vanduffel, Neil Vasdev, Guy BormansHeat shock protein 90 (Hsp90) is essential for maintaining cellular proteostasis and may play an important role in the development of neurodegenerative proteinopathies. Therefore, we aimed to develop an Hsp90-specific PET brain tracer to quantify Hsp90 expression in the brain in vivo in order to explore its potential as a biomarker for neurodegenerative disease characterization and to support Hsp90-targeted
-
First-in-Human Study of 18F-Labeled PET Tracer for Glutamate AMPA Receptor [18F]K-40: A Derivative of [11C]K-2 J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Sadamitsu Ichijo, Tetsu Arisawa, Mai Hatano, Waki Nakajima, Tomoyuki Miyazaki, Tsuyoshi Eiro, Yuuki Takada, Ryunosuke Iai, Akane Sano, Masaki Sonoda, Yutaro Takayama, Yuichi Kimura, Takuya TakahashiAlthough the alteration of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) distribution is believed to underlie physiologic and pathologic neuronal function, there has been no modality to evaluate AMPARs in a living human. [11C]K-2, the PET tracer we previously developed, is the first and only technology, to the best of our knowledge, to visualize AMPAR densities in
-
[18F]Florzolotau PET for the Differential Diagnosis of Parkinsonism in Patients with Suspected 4-Repeat Tauopathies J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Joachim Brumberg, Nils Schröter, Ganna Blazhenets, M. Aymen Omrane, Christian Volz, Cornelius Weiller, Michel Rijntjes, Lars Frings, Sabine Hellwig, Wolfgang H. Jost, Philipp T. MeyerThe second-generation tau radioligand [18F]florzolotau is a promising biomarker for 4-repeat (4R) tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), which are difficult to disentangle clinically. Prior studies evaluating the diagnostic accuracy of [18F]florzolotau PET focused on highly selected patient populations (e.g., PSP–Richardson syndrome or amyloid-β–negative
-
Initial Experience with Dual-Time-Point [18F]Flurpiridaz PET/CT for Localization of Parathyroid Adenomas in Primary Hyperparathyroidism J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Thorsten Derlin, Dennis Kleine-Döpke, Lavinia Neubert, Tobias L. Ross, Bastian P. Ringe, Moritz Schmelzle, Frank M. BengelWe aimed to evaluate the feasibility of [18F]flurpiridaz PET/CT for localization of parathyroid adenomas in patients with primary hyperparathyroidism (pHPT). Methods: Data for 11 patients with pHPT undergoing dual-time-point [18F]flurpiridaz PET/CT for localization of hyperfunctioning parathyroid glands were retrospectively analyzed. PET/CT findings were compared with results of other imaging tests
-
212Bi-Macroaggregated Albumin Inhibited Mouse Melanoma Growth by Regulating Cell Cycle Checkpoint Markers Without Promoting Living Cell Repopulation J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Satyendra Kumar Singh, Nathan Kauffman, Isabelle Maria Lynch, Zeynep Meral Kunt, Kurt R. Zinn, Dalen Agnew, Jinda FanRadiotherapy using an α-particle emitting radionuclide has emerged as a promising candidate for cancer treatment; however, the efficacy of 212Bi for mouse melanoma treatment has not yet been studied. Here, we evaluated the efficacy of 212Bi-labeled macroaggregated albumin (MAA) in delivering radiation to mouse melanoma cells in vitro and in vivo. Methods: The efficacy of 212Bi efficacy in killing melanoma
-
161Tb Radioimmunotherapy as a Treatment for CD30-Positive Lymphomas J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Elisa Rioja-Blanco, Yara Banz, Christoph Schlapbach, Urban Novak, Tanja Chiorazzo, Nicole L. Bertschi, Peter Bernhardt, Pascal V. Grundler, Nicholas P. van der Meulen, Michal Grzmil, Roger Schibli, Martin BeheLymphoma remains a significant health concern, necessitating innovative treatment approaches. 161Tb’s coemission of ultra-short-range conversion and Auger electrons, with its medium-energy β–-particles, may enable the elimination of single cells and small clusters present in circulation, improving therapeutic outcomes. In this study, we compared 161Tb radioimmunotherapy targeting CD30—a receptor overexpressed
-
Multicycle Dosimetric Behavior and Dose–Effect Relationships in [177Lu]Lu-DOTATATE Peptide Receptor Radionuclide Therapy J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Gunjan Kayal, Molly E. Roseland, Chang Wang, Kellen Fitzpatrick, David Mirando, Krithika Suresh, Ka Kit Wong, Yuni K. DewarajaWe investigated pharmacokinetics, dosimetric patterns, and absorbed dose (AD)–effect correlations in [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) for metastatic neuroendocrine tumors (NETs) to develop strategies for future personalized dosimetry-guided treatments. Methods: Patients treated with standard [177Lu]Lu-DOTATATE PRRT were recruited for serial SPECT/CT imaging. Kidneys were
-
First-in-Human Serum Stability Studies of [177Lu]Lu-AMTG: A Step Toward Improved GRPR-Targeted Radiopharmaceutical Therapy J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Veronika Felber, Nadine Holzleitner, Markus Joksch, Tim Suhrbier, Gunhild von Amsberg, Sarah Schwarzenböck, Jens Kurth, Martin Heuschkel, Thomas Günther, Bernd J. KrauseThe use of PET/CT with gastrin-releasing peptide receptor (GRPR) ligand [68Ga]Ga-AMTG has recently been shown to diagnose metastatic disease not detected by 18F-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer. This study aimed to analyze the serum stability of [177Lu]Lu-AMTG in human subjects due to the compound’s high stability observed preclinically and to elucidate its
-
Prostate Cancer Recurrence Due to Isolated Testicular Metastases Detected by PSMA PET/CT J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Mateus de Oliveira Taveira, Ali Aria Razmaria, Heiko Schoder, Randy YehProstate cancer is the most common solid malignancy to metastasize to the testicles, although testicular metastases remain rare and are often discovered only postmortem. Methods: Retrospective analysis of 95 68Ga-prostate-specific membrane antigen (PSMA) PET/CT reports from September 2016 to July 2024 using scrotal region search terms identified 30 patients with indeterminate findings and 6 patients
-
Determination of the Intralesional Distribution of Theranostic 124I-Omburtamab Convection-Enhanced Delivery in Treatment of Diffuse Intrinsic Pontine Glioma J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Alexandre França Velo, Alexandra Giantini Larsen, John L. Humm, Pat Zanzonico, Sofia Haque, Mark Souweidane, Neeta Pandit-TaskarThis phase 1, dose-escalation study examined the use of the radiolabeled antibody 124I-Omburtamab delivered directly to brain-stem tumors via convection-enhanced delivery (CED). CED bypasses the blood–brain barrier by injecting the agent under the pressure of a peristaltic pump to convectively drive the therapeutic agent through the brain tissue and tumor compartment, enabling high concentrations at
-
Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Justin S. Hachey, Tara D. Viray, Mattia Matasci, Domenico Ravazza, Dario Neri, Jason S. LewisTriple-negative breast cancer (TNBC) lags behind other breast cancer types in targeted therapeutic and diagnostic imaging agent development, largely due to high disease heterogeneity. Noninvasive imaging is essential for diagnosing and staging TNBC and predicting and measuring treatment response. This study targeted a conserved disease-specific extracellular matrix protein domain (the extra domain
-
Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Randy Yeh, Fresia Pareja, Parnian Shobeiri, Dara Ross, Vetri S. Jayaprakasam, Ali Aria Razmaria, Joshua Z. Drago, Audrey Mauguen, Serge K. Lyashchenko, Brian M. Zeglis, Jason S. Lewis, Gary A. UlanerTrastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted antibody–drug conjugate, demonstrated remarkable efficacy in previously treated patients with HER2-low metastatic breast cancer (mBC), marking a new therapeutic option for this patient population. Prior studies with HER2 PET using 89Zr-radiolabeled antibodies were limited by high rates of imaging false positives
-
CD70-Targeted [18F]RCCB6 Immuno-PET/CT Imaging in Patients with Nasopharyngeal Carcinoma: A Proof-of-Concept Study J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Binyu Shi, You Zhang, Shuo Wu, Dongsheng Xu, Qianyun Wu, Wenzhi Jia, Shuxian An, Cheng Wang, Yongrui Bai, Jianjun Liu, Junjun Zhou, Weijun WeiCD70 has emerged as a promising biomarker for nasopharyngeal carcinoma (NPC). This study investigated CD70 expression patterns in NPC specimens and evaluated the diagnostic potential of CD70-targeted [18F]RCCB6 immuno-PET/CT in patients with NPC. Methods: CD70 expression was analyzed in 80 archived NPC specimens and correlated with clinical and pathologic features. Using [18F]RCCB6, a single-domain
-
2024 SNMMI Highlights Lecture: Cardiovascular Sciences J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
James T. ThackerayThe Highlights Lecture, presented at the closing session of each SNMMI Annual Meeting, was originated and presented for more than 30 y by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. The 2024 Highlights Lectures were delivered
-
From Genome to Phenome: Opportunities and Challenges of Molecular Imaging J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Mei Tian, Leroy Hood, Arturo Chiti, Markus Schwaiger, Satoshi Minoshima, Yasuyoshi Watanabe, Keon Wook Kang, Hong ZhangThe study of the human phenome is essential for understanding the complexities of wellness and disease and their transitions, with molecular imaging being a vital tool in this exploration. Molecular imaging embodies the 4 principles of human phenomics: precise measurement, accurate calculation or analysis, well-controlled manipulation or intervention, and innovative invention or creation. Its application
-
Approaches to Imaging Immune Activation Using PET J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Ashwin Singh Parihar, Niharika Pant, Pedram Heidari, Lawrence Fong, Amir IravaniThis review explores the role of PET in imaging immune activation, particularly in oncology. 18F-FDG is widely used for assessing treatment response to immunotherapies and can demonstrate unique response patterns as well as immune-related adverse events. However, because of the limited specificity of 18F-FDG, newer PET radiopharmaceuticals targeting specific cellular or subcellular components of the
-
The Role of PSMA PET Parameters as Biomarkers for Response to PSMA-Targeted Radiopharmaceutical Therapy J Nucl. Med. (IF 9.1) Pub Date : 2025-06-01
Vishnu Murthy, Vinicius Ludwig, Andrei Gafita, Thomas A. Hope, Jeremie CalaisProstate-specific membrane antigen (PSMA) PET is a well-established imaging tool for the evaluation of primary and recurrent prostate cancer (PCa). 177Lu PSMA-targeted radiopharmaceutical therapy (RPT) enables direct delivery of β-radiation to PSMA-expressing PCa cells while minimizing damage to normal tissue. As PSMA RPT becomes more widely used, there is growing interest in evaluating the predictive
-
Granzyme B PET Imaging Predicts Response to Immunotherapy in a Diet-Induced Obesity Model of Breast Cancer J Nucl. Med. (IF 9.1) Pub Date : 2025-05-29
Shannon E. Lynch, Corinne Crawford, Addison L. Hunt, Luke L. Sligh, Yujun Zhang, Lyse A. Norian, Benjamin M. Larimer, Suzanne E. Lapi, Anna G. SoraceVisual Abstract
-
Whole-Body [18F]DPA-714 Kinetic Assessment Using PET/CT Scanner with Long Axial Field of View J Nucl. Med. (IF 9.1) Pub Date : 2025-05-29
Xavier Palard-Novello, Denise Visser, Maqsood Yaqub, Elsmarieke van de Giessen, Marijke E. den Hollander, Albert D. Windhorst, Sander C.J. Verfaillie, Hans Knoop, Bart N.M. van Berckel, Sandeep S.V. Golla, Nelleke Tolboom, Ronald BoellaardMultisystemic inflammation might be a key pathophysiologic mechanism in post–coronavirus disease 2019 (post-COVID) syndrome. N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a] pyrimidin-3-yl)acetamide ([18F]DPA-714), which binds with high affinity the translocator protein (TSPO) receptor, is used as a marker of inflammation. Therefore, quantifying [18F]DPA-714 uptake throughout the
-
Clinical Outcomes of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Skeletal Metastases from Neuroendocrine Tumors: Insights from Real-World Experience J Nucl. Med. (IF 9.1) Pub Date : 2025-05-29
Kunal Ramesh Chandekar, Swayamjeet Satapathy, Sanjana Ballal, Madhav Prasad Yadav, Shubha Gadde Ravindra, Sameer Rastogi, Ranjit Kumar Sahoo, Chandrasekhar BalSkeletal metastases portend a poor prognosis for patients with neuroendocrine tumors (NETs). Literature on peptide receptor radionuclide therapy (PRRT) specific to patients with skeletal metastases from NETs is scarce. This study assessed real-world clinical outcomes of 177Lu-DOTATATE PRRT in this patient subgroup. Methods: Data from consecutive patients with well-differentiated NETs and skeletal metastases
-
[18F]FDG PET/CT Predicts Patient Survival in Patients with Systemic Sclerosis–Associated Interstitial Lung Disease J Nucl. Med. (IF 9.1) Pub Date : 2025-05-29
David M.L. Lilburn, Helen S. Garthwaite, Balaji Ganeshan, Thida Win, Nicholas J. Screaton, Luke R. Hoy, Darren Walls, Raymond Endozo, Robert I. Shortman, Francesco Fraioli, Athol U. Wells, Christopher P. Denton, Ashley M. Groves, Joanna C. PorterVisual Abstract
-
Can 177Lu-DOTATATE Kidney Absorbed Doses be Predicted from Pretherapy SSTR PET? Findings from Multicenter Data J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Azadeh Akhavanallaf, Zhonglin Lu, Avery B. Peterson, Johan Blakkisrud, Sara Kurkowska, Surekha Yadav, Chang Wang, Carlos Uribe, Caroline Stokke, Arman Rahmim, Ka Kit Wong, Jean-Mathieu Beauregard, Thomas A. Hope, Katarina Sjögreen Gleisner, Yuni K. DewarajaBefore performing 177Lu-DOTATATE therapy for neuroendocrine tumors, somatostatin receptor (SSTR) PET imaging is currently used to confirm sufficient tumor SSTR expression, but it also has potential to be used to personalize treatment by predicting absorbed doses to critical organs. This study aims to validate the predictive capability of SSTR PET in anticipating renal absorbed dose in the first cycle
-
[18F]FDG Metabolic Tumor Volume as a Prognostic Marker in Neuroendocrine Neoplasm: A Multicenter Study J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
David L. Chan, Aimee Hayes, Ioannis Karfis, Alice Conner, Magdalena Mileva, Elizabeth Bernard, Shaunak Navalkissoor, Gopinath Gnanasekaran, Stephen J. Clarke, Paul J. Roach, Patrick Flamen, Martyn E. Caplin, Nick Pavlakis, Christos Toumpanakis, Dale L. Bailey[18F]FDG PET/CT avidity predicts higher-grade disease and worse prognosis in patients with metastatic neuroendocrine neoplasm. However, there is less evidence regarding the role of [18F]FDG-avid tumor volume in predicting prognosis. We planned to determine whether metabolic tumor volume (MTV) on [18F]FDG PET/CT predicts prognosis in patients with advanced gastroenteropancreatic neuroendocrine neoplasm
-
Rethinking Dosimetry: A European Perspective J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Johannes Tran-Gia, Francesco Cicone, Michel Koole, Francesco Giammarile, Jonathan Gear, Emmanuel Deshayes, Pablo Minguez Gabiña, Marta Cremonesi, Jonathan Wadsley, Peter Bernhardt, Manuel Bardiès, Silvano Gnesin, Mattias Sandström, Ulrike Garske-Román, Mona-Elisabeth R. Revheim, Frederik A. Verburg, Mark Konijnenberg, Bernd Joachim Krause, Michael Lassmann, Caroline StokkeRadiopharmaceutical therapy (RPT) is entering a new era of personalization, driven by advances in molecular imaging, radiopharmaceutical development, and a growing body of clinical evidence linking absorbed dose to treatment outcomes. Although external-beam radiotherapy has long integrated dosimetry into standard practice, RPT historically relied on fixed radiopharmaceutical activities and absorbed
-
Histologic Ex Vivo Validation of the [18F]SITATE Somatostatin Receptor PET Tracer J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Nils F. Trautwein, Sven Mattern, Martina Hinterleitner, Gerald Reischl, Ralf Schirrmacher, Volker Steger, Silvio Nadalin, Konstantin Nikolaou, Johannes Schwenck, Stephan Singer, Christian la FougèreRadiolabeled somatostatin analogs (SSAs), such as [68Ga]Ga-DOTA SSAs, have transformed imaging and therapeutic strategies. However, their use is constrained by the high cost of generators and their short half-life. In contrast, [18F]SITATE presents a promising alternative, offering the advantage of a longer half-life than 68Ga, along with the cost-effectiveness of cyclotron-based production. This study
-
Establishing In Vitro Dosimetric Models and Dose–Effect Relationships for 177Lu-DOTATATE in Neuroendocrine Tumors J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Giulia Tamborino, Pleun Engbers, Tijmen H. de Wolf, Thom G.A. Reuvers, Rob Verhagen, Mark Konijnenberg, Julie NonnekensVisual Abstract
-
Transarterial Radioembolization in the TACOME Trial: Dosimetric Analysis and Clinical Features in Predicting Response and Overall Survival J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Cigdem Soydal, Mine Araz, Burak Demir, Tunc Ones, Kerim Sonmezoglu, Nalan Alan Selcuk, Tugsan Balli, Emine Goknur Isık, Bilge Volkan Salancı, Erkan Derebek, Selin Kesim, Onur Erdem Sahin, Ferhat Can Piskin, Emre Can Celebioglu, Mehmet Sadik Bilgic, Nuriye Ozlem KucukIn this multicenter retrospective study, we aimed to analyze the dose–response and survival relationships and estimate the tumor absorbed radiation dose required to achieve response in colorectal cancer liver metastases treated with 90Y glass microspheres. Methods: Patients with metastatic colorectal cancer treated with 90Y glass microspheres were included in this retrospective study. Mean perfused
-
Retreatment of Metastatic Castration-Resistant Prostate Cancer Patients with 223Ra Therapy in Daily Practice J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Joost H.H.M. van Riel, Maarten L. Donswijk, Christel Brouwer, Winald R. Gerritsen, T.T. Ha Tan-Phan, Paul W.L. Thimister, Walter Noordzij, Erik T. Te Beek, Laurence J.C. van Warmerdam, Andries M. Bergman, Inge M. van Oort, Dirk N.J. Wyndaele, Maarten J. van der Doelen223Ra-dichloride (223Ra) is an approved therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have symptomatic bone metastases. After an initial course of 6 223Ra injections, treatment may be repeated. The purpose of this study was to evaluate the safety and efficacy of 223Ra retreatment of mCRPC in a real-world population. Methods: This multicenter, retrospective
-
177Lu-PSMA-617 Consolidation Therapy After Docetaxel in Patients with Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer: A Randomized, Phase 2 Trial J Nucl. Med. (IF 9.1) Pub Date : 2025-05-22
Swayamjeet Satapathy, Chandan K. Das, Shikha Goyal, Ashwani Sood, Kannan Periasamy, Piyush Aggarwal, Komal Preet, Shrawan K. Singh, Ravimohan S. Mavuduru, Girdhar S. Bora, Aditya P. Sharma, Gaurav Prakash, Rajender Kumar, Harmandeep Singh, Bhagwant R. Mittal177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617) has shown positive survival outcomes in metastatic castration-resistant prostate cancer. However, there are limited data in the hormone-sensitive setting. Here, in the CONSOLIDATE trial (177Lu-PSMA-617 Consolidation Therapy After Docetaxel in Patients with Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer), we intended
-
A Vision for Gastrin-Releasing Peptide Receptor Targeting for Imaging and Therapy: Perspective from Academia and Industry J Nucl. Med. (IF 9.1) Pub Date : 2025-05-15
Clément Morgat, Heying Duan, Simone Dalm, Elif Hindié, Thomas Günther, Bernd J. Krause, Vasko Kramer, Florine Cavelier, Andrew W. Stephens, Stephen Moran, Laura Lamb, Andrei IagaruThe gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers, including prostate cancer, breast cancer, small cell and non–small cell lung cancer, uterine and ovarian cancer, colon cancer, and gastrointestinal stromal tumors. This makes GRPR a multicancer target for theranostics, that is, molecular imaging and therapy. Here, we explore the current state of GRPR-targeted theranostics
-
Designed Ankyrin Repeat Protein–Mediated Peptide Nucleic Acid–Based Pretargeting: A Proof-of-Principle Study J Nucl. Med. (IF 9.1) Pub Date : 2025-05-15
Maryam Oroujeni, Kristina Westerlund, Eleftherios Papalanis, Alexander van Deventer, Yongsheng Liu, Jacob Clinton, Zhengyue Wang, Ivan Zelepukin, Anna Orlova, Vladimir Tolmachev, Amelie Eriksson KarlströmDesigned ankyrin repeat proteins (DARPins) are a class of engineered scaffold proteins (ESPs) with a molecular weight of approximately 15 kDa and a picomolar affinity for tumor antigen targets. Proof-of-concept studies have demonstrated the potential of DARPin radioimmunodiagnostics in humans. However, a high accumulation of activity in the kidneys limits their use in conventional radionuclide therapy
-
Theranostics in Perspective: White Paper J Nucl. Med. (IF 9.1) Pub Date : 2025-05-15
Marcel P.M. Stokkel, Martin Gotthardt, Ken Herrmann, Gopinath GnanasegaranNuclear medicine has evolved from a diagnostic-oriented speciality toward theranostics. Radionuclide therapy has become a booming business with newer radiopharmaceuticals and indications. Although the specialty of nuclear medicine seems scintillating, several challenges might limit sustained and long-term success. Some of the challenges and issues requiring clarification include radiopharmaceutical
-
[11C]Carfentanil PET Whole-Body Imaging of μ-Opioid Receptors: A First in-Human Study J Nucl. Med. (IF 9.1) Pub Date : 2025-05-08
Jacob G. Dubroff, Chia-Ju Hsieh, Corinde E. Wiers, Hsiaoju Lee, Alexander Schmitz, Elizabeth J. Li, Erin K. Schubert, Robert H. Mach, Henry R. Kranzlerμ-opioid receptors (MORs) are G-coupled receptors widely expressed in the brain and body. MORs have a high affinity for both endogenous opioids such as β-endorphins and exogenous opioids such as fentanyl. They mediate pain and reward and have been implicated in the pathophysiology of opioid, cocaine, and other substance use disorders. Using an instrument with a long axial field of view and the MOR-selective
-
[11C]ZTP-1: An Effective Short-Lived Radioligand for PET of Rat and Monkey Brain Phosphodiesterase Type 4 Subtype B J Nucl. Med. (IF 9.1) Pub Date : 2025-05-08
Qunchao Zhao, Jeih-San Liow, Joo Eun Jee, Jose Montero Santamaria, Matilah Pamie-George, Cheryl Morse, Shawn Wu, Sami S. Zoghbi, Sung Won Kim, Robert B. Innis, Victor W. Pike, Sanjay TeluPhosphodiesterase type 4 subtype B (PDE4B) selectively hydrolyzes cyclic adenosine monophosphate to enact numerous downstream signaling events. PDE4B is widely expressed in the brain and is implicated in several neuropsychiatric disorders. Moreover, PDE4B inhibition shows antiinflammatory and antidepressant-like effects in animal studies. [18F]PF-06445974 has been developed to image human brain PDE4B
-
Radiances of Cerenkov-Emitting Radionuclides on the In Vivo Imaging System J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Edwin C. Pratt, Travis M. Shaffer, David Bauer, Jason S. Lewis, Jan GrimmCerenkov (or Cherenkov) luminescence occurs when charged particles exceed the phase velocity of a given medium. Cerenkov as a modality has gained interest for visualization of numerous radionuclides. However, reported Cerenkov intensities are limited or provided as theoretic fluence estimates. Here, we present the largest experimental dataset of Cerenkov-emitting radionuclides using the in vivo imaging
-
Bioanalytic Hybrid System Merging 3-Dimensional Cell Culture and Chromatographic Precision for Unprecedented Preclinical Insights in Molecular Imaging J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Verena Pichler, Verena Schwingenschlögl-Maisetschläger, Irem Duman, Xavier Monforte, Stefanie Ponti, Lukas Zimmermann, Elma Joldic, Monika Dumanic, Chrysoula Vraka, Marcus Hacker, Christian Kraule, Andreas Herbert Teuschl-WollerWe introduce a unique bioanalytic hybrid system for the preclinical assessment of radiotracer candidates, combining a 3-dimensional cell culture on an artificial extracellular matrix functioning as a stationary phase and a chromatographiclike system array. Methods: Silk fibroin sponges were applied to simulate an extracellular matrix and to function as a stationary phase. Different cell lines were
-
Reduced Renal Uptake of Various Radiopharmaceuticals with Sodium Paraaminohippurate Coadministration in a Rat Model J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Marian Meckel, Stefanie Ehrenberg, Theresa Schmidt, Philipp Ritt, Margret I. Moré, Ralf Bergmann, Domokos Mathe, Konstantin ZhernosekovThe coinfusion of amino acids with targeted radiopharmaceutical therapy aims to reduce renal toxicity. Unfortunately, this requires a prolonged, large-volume infusion and often results in side effects such as nausea, vomiting, and hyperkalemia. Sodium paraaminohippurate is a nontoxic compound that has historically been used to measure renal plasma flow. It is excreted by the kidneys via glomerular
-
Measuring Total Metabolic Tumor Volume from 18F-FDG PET: A Reality Check J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Ronald Boellaard, Gerben J.C. Zwezerijnen, Irène Buvat, Laurence Champion, Narinée Hovhannisyan-Baghdasarian, Fanny Orlhac, Anne I.J. Arens, Daphne Lobeek, Filiz Celik, Cristina Mitea, Julia E. Huijbregts, Nelleke Tolboom, Bart de Keizer, Roelf Valkema, Floris H.P. van Velden, Petra Dibbets-Schneider, Sanne E. Wiegers, Pieternella J. Lugtenburg, Sally F. Barrington, Josée M. ZijlstraMeasuring total metabolic tumor volume (TMTV) on 18F-FDG PET/CT images in clinical practice requires a fast, reliable, and easy-to-perform multilesional segmentation workflow. We conducted a field test to derive total metabolic volumes using 5 representative baseline 18F-FDG PET/CT scans from patients with diffuse large B-cell lymphoma. The scans were transferred to 10 different sites or readers who
-
The Use of Maximum-Intensity Projections and Deep Learning Adds Value to the Fully Automatic Segmentation of Lesions Avid for [18F]FDG and [68Ga]Ga-PSMA in PET/CT J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Cláudia S. Constantino, Francisco P.M. Oliveira, Marisa Machado, Susana Vinga, Durval C. CostaThis study investigated the added value of using maximum-intensity projection (MIP) images for fully automatic segmentation of lesions using deep learning (DL) in [18F]FDG and [68Ga]Ga-prostate-specific membrane antigen (PSMA) PET/CT scans. Methods: We used 489 staging [18F]FDG PET/CT scans from patients diagnosed with melanoma, lymphoma, or lung cancer (391 scans for training and 98 for internal testing)
-
MHC-I–Driven Antitumor Immunity Counterbalances Low Absorbed Doses of Radiopharmaceutical Therapy J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Julie Constanzo, Aliasghar Parach, Timothee David, Joshua Karam, Frank Bruchertseifer, Alfred Morgenstern, Marta Jarlier, Manuel Bardiès, Emmanuel Deshayes, Amelie Gudin-de-Vallerin, Florence Boissière-Michot, Evelyne Lopez-Crapez, Jean-Pierre PougetPreclinical and clinical studies increasingly show that the immune response plays a major role in radiotherapy. Here, we investigated the role of major histocompatibility complex class I (MHC-I) molecules recognized by cytotoxic CD8+ T cells in the response to radiopharmaceutical therapy (RPT). Methods: Two murine melanoma cell lines that express low and high MHC-I levels (B16F10 and B16K1, respectively)
-
Characterization of Effective Half-Life for Instant Single-Time-Point Dosimetry Using Machine Learning J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Carlos Vinícius Gomes, Yizhou Chen, Isabel Rauscher, Song Xue, Andrei Gafita, Jiaxi Hu, Robert Seifert, Lorenzo Mercolli, Julia Brosch-Lenz, Jimin Hong, Marc Ryhiner, Sibylle Ziegler, Ali Afshar-Oromieh, Axel Rominger, Matthias Eiber, Thiago Viana Miranda Lima, Kuangyu ShiSingle-time-point (STP) image-based dosimetry offers a more convenient approach for clinical practice in radiopharmaceutical therapy (RPT) compared with conventional multiple-time-point image-based dosimetry. Despite numerous advancements, current STP methods are limited by the need for strict and late timing in data acquisition, posing challenges in routine clinical settings. This study introduces
-
Assessment of [177Lu]Lu-DOTATATE Dosimetry from High-Speed Whole-Body Recordings Provided by a 360° Cadmium–Zinc–Telluride Camera Compared with Results from a Conventional Anger-Camera Protocol J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Timothée Zaragori, Elodie Chevalier, Quentin Citerne, Véronique Roch, Gabriela Hossu, Pierre-Yves Marie, Caroline Boursier, Laetitia ImbertAbsorbed doses (ADs) may be calculated through serial conventional SPECT imaging after therapeutic [177Lu]Lu-DOTATATE injection but with recording times too long for clinical routine. The aim of this study was to determine whether activity concentrations and ADs calculated from a high-speed whole-body 360° cadmium–zinc–telluride (CZT) SPECT camera are comparable to those provided by conventional SPECT
-
Validating the Utility of Supervised Clustering Algorithm for Precise [11C]DPA-713 PET Brain Image Quantification J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Youjin Lee, Thanh D. Nguyen, Yong Du, Jennifer M. Coughlin, Sara A. Zein, Nicolas A. Karakatsanis, Sadek Nehmeh, Martin G. Pomper, Susan A. Gauthier, Yeona KangThe reliance of quantitative PET imaging on the arterial input function makes brain PET challenging to perform in certain populations, limiting the sample size. To address this challenge, a supervised clustering algorithm (SVCA) has been introduced as an alternative. Our objective was to validate SVCA’s performance for brain PET with [11C]DPA-713 that targets a putative marker of brain injury and repair
-
Consensus Nomenclature for Radionuclide Therapy: Initial Recommendations from Nuclear Medicine Global Initiative J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Akram Al-Ibraheem, Andrew M. Scott, Ahmed Saad Abdlkadir, Alexis Vrachimis, Francois Lamoureux, Patricia Bernal Trujillo, Dale L. Bailey, Stuart More, Francesco Giammarile, Rakesh Kumar, Julie Nonnekens, Cathy S. Cutler, Jean-Luc C. Urbain, Elizabeth H. Dibble, Mike Machaba Sathekge, Jamshed Bomanji, Juliano J. Cerci, Elizabeth Thomas, William Small, Lizette Louw, Joo Hyun O, Sze Ting Lee, Helen NadelSince its inception in 2012, the Nuclear Medicine Global Initiative (NMGI) of the Society of Nuclear Medicine and Molecular Imaging has played an important role in addressing significant challenges in the field of nuclear medicine and molecular imaging. The first 3 projects were dedicated to standardizing pediatric nuclear medicine practices, addressing the global challenges of radionuclide access
-
Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Lidia Strigari, Jazmin Schwarz, Tyler Bradshaw, Julia Brosch-Lenz, Geoffrey Currie, Georges El-Fakhri, Abhinav K. Jha, Signe Mežinska, Neeta Pandit-Taskar, Emilie Roncali, Kuangyu Shi, Carlos Uribe, Tahir Yusufaly, Habib Zaidi, Arman Rahmim, Babak SabouryComputational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by
-
Dansylated Amino Acid–Modified Long-Acting PSMA Derivatives 68Ga/177Lu-LNC1011 as Prostate Cancer Theranostics J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Hongzhang Yang, Jiarou Wang, Xuejun Wen, Huifeng Guo, Vivianne Jakobsson, Tianzhi Zhao, Fantian Zeng, Huaxiang Shen, Heng Zhang, Xiaomin Liu, Yatong Qin, Xinyi Li, Hehe Xiong, Zijian Zhou, Jingjing Zhang, Xiaoyuan ChenProstate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy has demonstrated promising potential for treating metastatic castration-resistant prostate cancer. Recently, albumin-binding motif-modified PSMA radioligands with prolonged blood circulation were developed to improve tumor uptake and therapeutic effectiveness, properties which, however, were associated with an increased
-
First-in-Human Phase 0 Study of AB001, a Prostate-Specific Membrane Antigen–Targeted 212Pb Radioligand, in Patients with Metastatic Castration-Resistant Prostate Cancer J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Kjetil Berner, Eivor Hernes, Monika Kvassheim, Mona-Elisabeth Revheim, Julie Bastiansen, Silje Selboe, Charlotte L. Bakken, Simen R. Grønningsæter, Øyvind S. Bruland, Roy H. Larsen, Lily Bouzelmat, Vicki L. Jardine, Caroline StokkeAB001, a prostate-specific membrane antigen (PSMA)–targeted small molecule labeled with the in vivo–generating α-emitter 212Pb, was investigated in a phase 0 trial in patients with metastatic castration-resistant prostate cancer (mCRPC). The primary objective was to explore the feasibility of -camera imaging to assess biodistribution and uptake in metastatic lesions. Methods: Three patients with progressive
-
PET- and CT-Based Imaging Criteria for Response Assessment of Gastroenteropancreatic Neuroendocrine Tumors Under Radiopharmaceutical Therapy J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Felix L. Herr, Christian Dascalescu, Matthias P. Fabritius, Gabriel T. Sheikh, Mathias J. Zacherl, Vera Wenter, Lena M. Unterrainer, Matthias Brendel, Adrien Holzgreve, Christoph J. Auernhammer, Christine Spitzweg, Tanja Burkard, Jens Ricke, Maurice M. Heimer, Clemens C. CyranDespite well-documented limitations, current guidelines recommend the use of size-based RECIST 1.1 for response assessment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) under radiopharmaceutical therapy (RPT). We hypothesize that functional criteria are superior to RECIST 1.1 for response assessment and progression-free survival (PFS) prediction, and molecular scores can be used in prognosticating
-
Additive Value of [68Ga]Ga-RM26 PET/CT to [68Ga]Ga-PSMA-617 PET/CT in Detecting Pelvic Lymph Node Metastasis in Prostate Cancer: A Prospective, Single-Center, Phase II Study J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Wei Tang, Lin Qi, Minfeng Chen, Ye Zhang, Yongxiang Tang, Shuo Hu, Xiaomei Gao, Yi CaiLymph node staging in prostate cancer is crucial for treatment and prognosis, yet [68Ga]Ga-PSMA-617 PET/CT has limited sensitivity in detecting pelvic lymph node metastasis (PLNM). [68Ga]Ga-RM26 PET/CT, targeting the gastrin-releasing peptide receptor, complements [68Ga]Ga-PSMA-617 PET/CT in assessing primary tumor extension and aggressiveness. However, its role in detecting PLNM and complementing
-
Prevalence and Medium-Term Outcomes of Patients with Biopsy-Proven Intermediate- to High-Risk Prostate Adenocarcinoma with Low Intraprostatic Uptake on [68Ga]Ga-PSMA-11 PET/CT in the proPSMA Study J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
David C. Chen, James P. Buteau, Louise Emmett, Ramin Alipour, Felipe de Galiza Barbosa, Matthew J. Roberts, Aoife McVey, Jonathan O’Brien, Sidney Levy, Roslyn J. Francis, Nathan Lawrentschuk, Declan G. Murphy, Michael S. HofmanThe current prevalence of low intraprostatic uptake for staging prostate-specific membrane antigen (PSMA) PET ranges between 4.4% and 17% in retrospective studies. We aimed to define the prevalence and describe the outcomes of patients with low intraprostatic uptake on PSMA PET/CT in the prospective proPSMA study. Methods: We identified patients with an SUVmax of 4 or less on PSMA PET/CT in the proPSMA
-
177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Andreas Hallqvist, Elva Brynjarsdóttir, Tomas Krantz, Marie Sjögren, Johanna Svensson, Peter BernhardtThis phase I trial aimed to assess the feasibility and toxicity of combining the poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib with 177Lu-DOTATATE in patients with somatostatin receptor–positive tumors, with the goal of enhancing treatment efficacy through the inhibition of tumor cell DNA repair mechanisms. Methods: Eighteen patients were enrolled, mostly with pancreatic or small
-
Diagnostic Potential of 68Ga-NeoB PET/CT with Estrogen Receptor– and Progesterone Receptor–Positive Breast Cancer Undergoing Staging or Restaging for Metastatic Disease J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Zahra Sabahi, Andrew Nguyen, Keith Wong, Sherrington Li, Nathan Papa, Elgene Lim, Rachel F. Dear, Alexander M. Menzies, Frances Boyle, Yoland Antill, Belinda E. Kiely, Benjamin C. Forster, Cindy Mak, Diana Adams, Lina Pugliano, Andrew Spillane, Shikha Sharma, Adam Hickey, Aron Poole, Shikha Agrawal, Sobia Khan, Narjess Ayati, Louise Emmett18F-FDG PET/CT has low sensitivity for estrogen receptor and progesterone receptor (ER/PR)–positive breast cancer. By contrast, gastrin-releasing peptide receptor is overexpressed in ER/PR-positive breast cancer. This study assessed the diagnostic potential of 68Ga-NeoB PET/CT in staging or restaging metastatic ER/PR-positive and human epidermal growth factor receptor 2 (HER2)–negative breast cancer
-
18F-Fluoroestradiol PET/CT for Predicting Benefit from Endocrine Therapy in Patients with Estrogen Receptor–Positive Breast Cancer: A Systematic Review and Metaanalysis J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Ashwin Singh Parihar, Sofia Vaz, Siobhan Sutcliffe, Niharika Pant, Jan W. Schoones, Gary A. Ulaner18F-fluoroestradiol (18F-FES) PET/CT has been investigated as a potential biomarker to predict response to endocrine therapies in patients with estrogen receptor (ER)–positive breast cancer. Although previous findings were promising, most had limited statistical significance because of small individual sample sizes. Therefore, we performed a systematic review and metaanalysis of the 18F-FES PET/CT
-
Tumor Asphericity in FDG PET Is an Independent Prognostic Parameter Improving Risk Stratification in Patients with Head and Neck Squamous Cell Carcinoma J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Patrick Hausmann, Sebastian Zschaeck, Christian Furth, Pavel Nikulin, Paulina Cegla, Siyer Roohani, Elia Lombardo, Joanna Kazmierska, Nathalie L. Albert, Adrien Holzgreve, Iosif Strouthos, Claus Belka, Guillaume Landry, Witold Cholewinski, Jorg Kotzerke, Michael Baumann, Mechthild Krause, Daniel Zips, Jörg van den Hoff, Frank HofheinzTumor asphericity in 18F-FDG PET is a prognostic marker that has been investigated in small pilot studies of patients with head and neck squamous cell carcinoma (HNSCC). Here, we investigated the prognostic role of asphericity in a large multicenter database of patients with HNSCC treated with primary radiotherapy or chemoradiation and assessed its independent prognostic value. Methods: In total, 1
-
Imaging the Activity of Efflux Transporters at the Blood–Brain Barrier in Neurologic Diseases: Radiotracer Selection Criteria J Nucl. Med. (IF 9.1) Pub Date : 2025-05-01
Nicolas Tournier, Oliver LangerEfflux transporters of the adenosine triphosphate–binding cassette (ABC) superfamily, such as P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), are highly expressed at the blood–brain barrier (BBB), where they contribute to maintaining brain homeostasis. P-gp may serve as an imaging biomarker to assess the contribution of BBB functionality rather than integrity to the onset