The Journal of Nuclear Medicine最新文献

{"title":"Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins","authors":"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 Saboury","doi":"10.2967/jnumed.124.268186","DOIUrl":"https://doi.org/10.2967/jnumed.124.268186","url":null,"abstract":"<p>Computational 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 real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT. To this aim, the major social, ethical, and regulatory challenges related to TDT implementation and adoption have been analyzed. <b>Methods:</b> The artificial intelligence&ndash;dosimetry working group of the Society of Nuclear Medicine and Molecular Imaging is actively proposing, motivating, and developing the field of computational nuclear oncology, a unified set of scientific principles and mathematic models that describe the hierarchy of etiologic mechanisms involved in RPT dose response. The major social, ethical, and regulatory challenges to realize TDTs have been highlighted from the literature and discussed within the working group, and possible solutions have been identified. <b>Results:</b> This technology demands the implementation of advanced computational tools, harmonized and standardized collection of large real-time data, and modeling protocols to enable interoperability across institutions. However, current legislations limit data sharing despite TDTs&rsquo; benefiting from such data. Although anonymizing data is often sufficient, ethical concerns may prevent sharing without patient consent. Approaches such as seeking ethical approval, adopting federated learning, and following guidelines can address this issue. Accurate and updated data input is crucial for reliable TDT output. Lack of reimbursement for data processing in treatment planning and verification poses an economic barrier. Ownership of TDTs, especially in interconnected systems, requires clear contracts to allocate liability. Complex contracts may hinder TDT implementation. Robust security measures are necessary to protect against data breaches. Cross-border data sharing complicates risk management without a global framework. <b>Conclusion:</b> A mechanism-based TDT framework can guide the community toward personalized dosimetry-driven RPT by facilitating the information exchange necessary to identify robust prognostic or predictive dosimetry and biomarkers. Although the future is bright, we caution that care must be taken to ensure that TDT technology is implemented in a socially responsible manner.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrapatient 16α-[18F]Fluoro-17β-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor–Positive Metastatic Breast Cancer","authors":"Jasper J.L. van Geel, Jasmine Moustaquim, Jorianne Boers, Sjoerd G. Elias, Esther M.M. Smeets, Jelijn J. Knip, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Geke A.P. Hospers, Michel van Kruchten, Marcel Stokkel, Daniela E. Oprea-Lager, Willemien C. Menke-van der Houven van Oordt, Elisabeth G.E. de Vries, Carolina P. Schröder","doi":"10.2967/jnumed.124.268984","DOIUrl":"https://doi.org/10.2967/jnumed.124.268984","url":null,"abstract":"<p>Intrapatient heterogeneity of estrogen receptor (ER) expression on 16α-[¹⁸F]fluoro-17β-estradiol ([¹⁸F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [¹⁸F]FES PET heterogeneity score (i.e., percentage of [¹⁸F]FES-positive metastases) was validated as a prognostic factor for endocrine therapy response and survival in a large cohort of patients with newly diagnosed MBC. Furthermore, we explored 2 less laborious methods to predict the [¹⁸F]FES PET heterogeneity score. <strong>Methods:</strong> Patients with ER-positive MBC included in the IMPACT-MBC study, who received baseline [¹⁸F]FES and [¹⁸F]FDG PET and first-line endocrine therapy, were included in this subanalysis. ER homogeneous (100% [¹⁸F]FES-positive lesions) and ER heterogeneous (both [¹⁸F]FES-positive and [¹⁸F]FES-negative lesions) MBC was distinguished by manual segmentation of all lesions on [¹⁸F]FES PET and related to progression-free survival (PFS) and overall survival (OS). In addition, the positive predictive value of the visual assessment and the 5-largest-lesions assessment to predict homogeneous MBC in all lesions on [¹⁸F]FES PET was determined. <strong>Results:</strong> From the 102 MBC patients eligible for the present retrospective subanalysis, 46 had ER homogeneous MBC and 56 had ER heterogeneous MBC. Differences were found between ER homogeneous and ER heterogeneous MBC for median PFS (19.8 vs. 15.0 mo; hazard ratio, 0.63; 95% CI, 0.41–0.96; <em>P</em> = 0.03) and median OS (62.5 vs. 34.7 mo; hazard ratio, 0.65; 95% CI, 0.38–1.08; <em>P</em> = 0.09). Twenty-one (38%) of 61 patients with ER homogeneous MBC by visual analysis and 37 (45%) of 83 patients with ER homogeneous MBC by the 5-largest-lesions method had ER heterogeneous MBC by manual segmentation of all lesions on [¹⁸F]FES PET (positive predictive value, 0.66 and 0.55, respectively). <strong>Conclusion:</strong> Patients with ER-positive homogeneous MBC showed a trend toward superior PFS and OS compared with patients with ER heterogeneous MBC. This analysis confirmed and validated the prognostic value of the [¹⁸F]FES PET heterogeneity score for endocrine therapy response and survival in a large cohort of MBC patients. The less laborious visual and 5-largest-lesions methods were inferior compared with assessment based on the [¹⁸F]FES PET heterogeneity score in all lesions.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation","authors":"Xuefeng Yan, Martin Noergaard, Cheryl L. Morse, Jeih-San Liow, Jinsoo Hong, Douglas Greve, Sanjay Telu, Min-Jeong Kim, Jose A. Montero Santamaria, Anthony Galassi, Ningping Feng, Sarah K. Williams Avram, Ted B. Usdin, Shawn Wu, Andrea Zhang, Lester S. Manly, Madeline Jenkins, Maia Van Buskirk, Adrian Lee, Sami S. Zoghbi, Victor W. Pike, Paolo Zanotti-Fregonara, Robert B. Innis","doi":"10.2967/jnumed.124.268525","DOIUrl":"https://doi.org/10.2967/jnumed.124.268525","url":null,"abstract":"<p>Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [¹¹C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)-<em>N</em>-(thiophen-2-ylmethyl)pyrimidin-4-amine ([¹¹C]MC1) to detect COX-2 density in a healthy human brain. <strong>Methods:</strong> The specificity of [¹¹C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human <em>COX-2</em> gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents. Twenty-seven healthy participants were injected with [¹¹C]MC1. Ten of these participants received 2 PET scans: a baseline study followed by blockade with celecoxib (600 mg orally), a preferential COX-2 inhibitor. Seventeen participants underwent test–retest imaging. All scans included concurrent arterial sampling. The tissue-to-plasma ratio at equilibrium (i.e., total distribution volume) was determined using a 2-tissue compartment model (2TCM). <strong>Results:</strong> In humanized transgenic COX-2 mice, 70%–90% of [¹¹C]MC1 brain uptake was blocked by nonradioactive MC1 and celecoxib (a COX-2 selective inhibitor) but not by PS13 (a COX-1 selective inhibitor), thereby confirming specific binding to human COX-2. Radioactivity in the human brain peaked at a concentration of about 4.0 SUV, indicating good passage through the blood–brain barrier. Values for the total distribution volume achieved stability after 80 min, indicating no radiometabolite contamination. Celecoxib reduced radioligand binding in neocortical areas by 25% but had little or no effect in subcortical regions and the cerebellum, which correlated with COX-2 messenger RNA expression levels. Binding site occupancy by celecoxib was virtually complete, as determined by the Lassen plots. Test–retest reliability was moderate (intraclass correlation coefficient, 0.65) but had relatively large variability (absolute retest variability, 20%). Reference tissue methods yielded results comparable to those of 2TCM but reduced retest variability by up to 75% and reduced intersubject variability (coefficient of variation) by about half. Thus, compared with 2TCM, which requires arterial blood, the reference tissue method is expected to significantly reduce the sample sizes required to detect statistically significant differences between groups. <strong>Conclusion:</strong> [¹¹C]MC1 has adequate sensitivity to measure the low density of COX-2 in a healthy human brain, suggesting it can also quantify the COX-2 elevations expected in human disorders associated with neuroinflammation.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"216 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Nuclear Medicine and Radiotheranostics","authors":"Patrick Veit-Haibach, Ken Herrmann, Richard Zimmermann, Roland Hustinx","doi":"10.2967/jnumed.124.268928","DOIUrl":"https://doi.org/10.2967/jnumed.124.268928","url":null,"abstract":"<p>There is a significantly growing interest in diagnostic and therapeutic radiopharmaceuticals, and it is foreseeable that an unprecedented number of patients will need to be treated with new nuclear medicine therapies. This predicted increase will have potentially significant environmental impacts. In this discussion, we show different areas of impact, as well as possible measures to reduce such impact. These measures may impact areas from the entire supply chain, starting at the production site of medical isotopes, the energy supply needed for production, transportation, and adaption of the injected amounts of radiopharmaceuticals in clinical use. Furthermore, arguments of local versus centralized production, potentially increasing or decreasing nuclear medicine procedures versus other greenhouse gas–emitting medical imaging tests, as well as radiopharmaceutical waste handling implications, are summarized and weighed against the current status. Overall, this summary hopefully serves as a basis for further discussion in the nuclear medicine community, potentially increases awareness of the environmental impact of this exciting medical field, and may even lead to implementation of measures.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total-Body PET System Designs with Axial and Transverse Gaps: A Study of Lesion Quantification and Detectability","authors":"Min Gao, Margaret E. Daube-Witherspoon, Joel S. Karp, Suleman Surti","doi":"10.2967/jnumed.124.267769","DOIUrl":"https://doi.org/10.2967/jnumed.124.267769","url":null,"abstract":"<p>High-sensitivity total-body PET enables faster scans, lower doses, and dynamic multiorgan imaging. However, the higher system cost of a scanner with a long axial field of view (AFOV) hinders its wider application. This paper investigates the impact on the lesion quantification and detectability of cost-effective total-body PET sparse designs. <strong>Methods:</strong> Using the PennPET Explorer (PPEx) as a model, 3 sparse configurations with the same 142-cm AFOV were considered, including designs with only axial gaps (AGs), only transverse gaps (TGs), and a mixture of AGs and TGs (MG), with retained detector fractions (DFs) ranging from 71% to 40%. Human data from the PPEx were used to emulate sparse designs by discarding lines of response as a proxy for missing detectors. We embedded lesion events in the resultant list data with varying uptakes in the lung and liver before reconstruction. A generalized scan statistics methodology was used to measure lesion detectability and quantification as a function of lesion uptake and scan duration. <strong>Results:</strong> Relative to a fully populated system, an AG design with 71% performs well but is susceptible to image artifacts as the DF decreases to 58%. A TG design performs well with a DF of 58% but requires twice the scan time to achieve similar lesion detectability and is susceptible to transverse field-of-view truncation below 60 cm as the DF is further decreased. An MG design with a DF of 58% requires 3 times the scan time to achieve similar lesion detectability, and with no evidence of artifacts even as the DF is decreased to 40%. <strong>Conclusion:</strong> Sparse designs with artifact-free images can provide comparable lesion quantification and detectability to the fully populated PPEx after compensating for the reduced sensitivity with increased scan time. Because an AG design is more susceptible to image artifacts with a lower DF, a system with only AGs is not an optimal choice for dramatic cost reduction. A TG design provides a higher relative sensitivity than AG or MG designs for a given DF, leading to a shorter scan time to achieve comparable lesion detectability. However, the increased truncation of the transverse field of view with decreasing DF limits this design choice. An MG design allows for the greatest cost reduction (lowest DF) if the scan duration is increased to compensate for the higher loss in sensitivity. Sparse designs of PET with a long AFOV provide a technologic solution for introducing such systems at reduced cost into routine clinical use.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RadioFlow Cytometry Reveals That [18F]FDG Uptake in K-RAS Lung Cancer Is Driven by Immune Cells: An Analysis on a Single-Cell Level","authors":"Chrysoula Vraka, Monika Homolya, Öykü Özer, Andreas Spittler, Michael Machtinger, Herwig P. Moll, Emilio Casanova, Claudia Kuntner, Stefan Grünert, Marcus Hacker, Cécile Philippe","doi":"10.2967/jnumed.124.268799","DOIUrl":"https://doi.org/10.2967/jnumed.124.268799","url":null,"abstract":"<p>Tumor metabolism is a hallmark of cancer, yet cellular heterogeneity within the tumor microenvironment presents a significant challenge, as bulk analysis masks the diverse metabolic profiles of individual cell populations. This complexity complicates our understanding of [¹⁸F]FDG uptake by distinct cell types in the tumor microenvironment. This study aims to investigate [¹⁸F]FDG uptake at the single-cell level in the lung of Kirsten rat sarcoma virus–driven cancer mouse models using the novel technique radio–flow cytometry (radioFlow). <strong>Methods:</strong> Two Kirsten rat sarcoma virus–driven lung cancer mouse models were injected with [¹⁸F]FDG for small-animal PET/CT and subsequent fluorescence-activated cell sorting of the lung. For radioFlow, the sorted cell fractions were then measured in a γ-counter and their radioactivity was normalized to the number of cells. <strong>Results:</strong> RadioFlow analysis of the lung tissue of both models showed a robust cell type–specific uptake pattern across experiments. Our key findings indicate that the [¹⁸F]FDG PET signal predominantly derives from immune cells (CD45⁺, F4/80⁻, 78.3% ± 6.6%; macrophage, 13.9% ± 4.3%), whereas tumor cells contributed only with 2.8% ± 1.0%, similar to the uptake of structural cells (CD45⁻; tumor cells, 5.0% ± 2.3%). Normalization showed that macrophages exhibited the highest glucose metabolism in both tumor models (57% ± 8%), followed by the remaining immune cells (27% ± 3%). <strong>Conclusion:</strong> These findings highlight the critical influence of immune cell metabolism on [¹⁸F]FDG imaging, emphasizing the need to account for immune contributions when interpreting [¹⁸F]FDG imaging in cancer.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large Language Models and Large Multimodal Models in Medical Imaging: A Primer for Physicians","authors":"Tyler J. Bradshaw, Xin Tie, Joshua Warner, Junjie Hu, Quanzheng Li, Xiang Li","doi":"10.2967/jnumed.124.268072","DOIUrl":"https://doi.org/10.2967/jnumed.124.268072","url":null,"abstract":"<p>Large language models (LLMs) are poised to have a disruptive impact on health care. Numerous studies have demonstrated promising applications of LLMs in medical imaging, and this number will grow as LLMs further evolve into large multimodal models (LMMs) capable of processing both text and images. Given the substantial roles that LLMs and LMMs will have in health care, it is important for physicians to understand the underlying principles of these technologies so they can use them more effectively and responsibly and help guide their development. This article explains the key concepts behind the development and application of LLMs, including token embeddings, transformer networks, self-supervised pretraining, fine-tuning, and others. It also describes the technical process of creating LMMs and discusses use cases for both LLMs and LMMs in medical imaging.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET-Based Risk Stratification in Primary Mediastinal B-Cell Lymphoma: A Comparative Analysis of Different Segmentation Methods in the IELSG37 Trial Patient Cohort","authors":"Luca Ceriani, Lisa Milan, Maria Cristina Pirosa, Maurizio Martelli, Teresa Ruberto, Luciano Cascione, Peter W.M. Johnson, Andrew J. Davies, Giovannino Ciccone, Emanuele Zucca","doi":"10.2967/jnumed.124.268874","DOIUrl":"https://doi.org/10.2967/jnumed.124.268874","url":null,"abstract":"<p>Standardizing tumor measurement on ¹⁸F-FDG PET is crucial for the routine clinical use of powerful PET-derived lymphoma prognostic factors such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The recent proposal of an SUV of 4 as a new reference segmentation threshold for most aggressive lymphomas may homogenize volume-based metrics and facilitate their clinical application. <strong>Methods:</strong> This study compared MTV and TLG in primary mediastinal B-cell lymphoma (PMBCL) patients estimated using an SUV of 4 and the current threshold at 25% of SUV_max. Baseline PET metrics were evaluated in 501 PMBCL patients from the IELSG37 trial. <strong>Results:</strong> Median MTV and TLG estimated with the 25% of SUV_max threshold were significantly lower than those obtained with the new reference threshold; however, an extremely high correlation was observed between the methods for both MTV (<em>r</em> = 0.95) and TLG (<em>r</em> = 0.99), resulting in superimposable prognostic power. <strong>Conclusion:</strong> These findings support the routine use of an SUV of 4 for volumetric measurements in PMBCL.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET/CT with Myocardial Blood Flow Assessment Is Prognostic of Cardiac Allograft Vasculopathy Progression and Clinical Outcomes","authors":"Nikil Prasad, Erin Harris, Ersilia M. DeFilippis, Gabriel Sayer, Margarita Chernovolenko, Paolo C. Colombo, Justin Fried, David Bae, Kyung Taek Oh, Jayant Raikhelkar, Sambhavi Sneha Kumar, Melana Yuzefpolskaya, Veli K. Topkara, Michelle Castillo, Elaine Y. Lam, Farhana Latif, Koji Takeda, Nir Uriel, Andrew J. Einstein, Kevin J. Clerkin","doi":"10.2967/jnumed.124.268713","DOIUrl":"https://doi.org/10.2967/jnumed.124.268713","url":null,"abstract":"<p>Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial vessels and microvasculature and remains a leading cause of posttransplant morbidity and mortality. This study examined the prognostic value and outcomes of CAV, assessed by ¹³N-ammonia PET/CT myocardial perfusion imaging in heart transplant recipients. <strong>Methods:</strong> PET/CT and invasive coronary angiography (ICA) were graded using validated scales. CAV progression was assessed using intrapatient sequences: baseline ICA, interval PET/CT with myocardial blood flow reserve, and subsequent ICA. Intervals between ICAs of 600, 900, and 1200 d were included, and for each, the negative predictive value (NPV) of CAV development was assessed. <strong>Results:</strong> In total, 344 heart transplant recipients underwent PET/CT for CAV assessment with a median follow-up of 4.8 y. PET CAV grade 0/1 had an NPV of 0.93, 0.95, and 0.95 at each respective time point for developing an International Society for Heart and Lung Transplantation CAV 2/3 on subsequent ICA. Compared with PET CAV 0, PET CAV 2/3 was associated with a 2.9-fold increased risk of all-cause mortality (hazard ratio, 2.86; 95% CI, 1.36–6.00; <em>P</em> = 0.006). PET CAV 1 had a numerically increased risk (hazard ratio, 2.03; 95% CI, 0.99–4.15; <em>P</em> = 0.054). In a sensitivity analysis of 135 patients with stable International Society for Heart and Lung Transplantation CAV over successive ICA, PET CAV 2/3 remained associated with increased risk of death or retransplantation (hazard ratio, 3.20; 95% CI, 1.18–8.69; <em>P</em> = 0.03). <strong>Conclusion:</strong> Noninvasive CAV assessment by PET/CT and myocardial blood flow reserve provides prognostic information and robust NPVs for development of moderate to severe CAV over intervals up to 4 y. These data suggest that, for certain patients, intervals between invasive screenings may be extended.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Biodistribution, and Radiation Dosimetry of the 68Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors","authors":"Elisabeth von Guggenberg, Gianpaolo di Santo, Christian Uprimny, Steffen Bayerschmidt, Boris Warwitz, Anton A. Hörmann, Taraneh S. Zavvar, Christine Rangger, Clemens Decristoforo, Anna Sviridenko, Bernhard Nilica, Giulia Santo, Irene J. Virgolini","doi":"10.2967/jnumed.124.268877","DOIUrl":"https://doi.org/10.2967/jnumed.124.268877","url":null,"abstract":"<p>Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the ⁶⁸Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH₂ (⁶⁸Ga-DOTA-MGS5). <strong>Methods:</strong> Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of ⁶⁸Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. <strong>Results:</strong> The administration of ⁶⁸Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. ⁶⁸Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in ⁶⁸Ga-DOTA-MGS5 PET/CT. <strong>Conclusion:</strong> Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for ⁶⁸Ga-DOTA-MGS5.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}