Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

{"title":"CD38-Targeted ⁸⁹Zr-DFO-Daratumumab PET of Myeloma: Immuno-PET Impacting Clinical Care.","authors":"Gary A Ulaner, Jason Lewis, Ola Landgren","doi":"10.2967/jnumed.124.269393","DOIUrl":"10.2967/jnumed.124.269393","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"482"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070466","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":"A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal Uptake of Para-Chloro-2-[¹⁸F]Fluoroethyletomidate in Healthy Volunteers and Patients with Primary Aldosteronism.","authors":"Daniel Gillett, Russell Senanayake, James MacFarlane, Waiel Bashari, August Palma, Lihua Hu, Ines Harper, Iosif A Mendichovszky, Gunnar Antoni, Per Hellman, Anders Sundin, Matthew Hird, István Boros, Morris J Brown, Heok Cheow, Luigi Aloj, Franklin Aigbirhio, Mark Gurnell","doi":"10.2967/jnumed.124.268425","DOIUrl":"10.2967/jnumed.124.268425","url":null,"abstract":"<p><p>Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [¹¹C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [¹¹C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the ¹⁸F-labeled analog, para-chloro-2-[¹⁸F]fluoroethyletomidate ([¹⁸F]CETO). <b>Methods:</b> We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [¹⁸F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [¹⁸F]CETO administration. The biodistribution of [¹⁸F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [¹⁸F]CETO uptake by normal adrenal tissue and APAs was also assessed. <b>Results:</b> Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [¹⁸F]CETO administration. [¹⁸F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [¹⁸F]CETO uptake by normal adrenal tissue. <b>Conclusion:</b> [¹⁸F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [¹⁸F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [¹⁸F]CETO uptake by normal glands. This positions [¹⁸F]CETO as a promising imaging tool for evaluation in the context of PA.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"434-440"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070449","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":"Advancing Tomorrow's Cancer Medicines: Jacob Van Naarden Talks with Ken Herrmann and Johannes Czernin About Corporate Approaches to New Therapeutics Development.","authors":"Jacob S Van Naarden, Ken Herrmann, Johannes Czernin","doi":"10.2967/jnumed.124.269354","DOIUrl":"10.2967/jnumed.124.269354","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"337-339"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030581","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":"Reply: A Comment on \"Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study\".","authors":"Gerhard Dahlhoff","doi":"10.2967/jnumed.124.269115","DOIUrl":"10.2967/jnumed.124.269115","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"485"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416643","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":"Dopaminergic Mechanisms of Cognitive Flexibility: An [¹⁸F]Fallypride PET Study.","authors":"Isabelle Miederer, Hans-Georg Buchholz, Lena Rademacher, Cindy Eckart, Dominik Kraft, Markus Piel, Christian J Fiebach, Mathias Schreckenberger","doi":"10.2967/jnumed.124.268317","DOIUrl":"10.2967/jnumed.124.268317","url":null,"abstract":"<p><p>Cognitive flexibility is the ability to appropriately adapt one's thinking and behavior to changing environmental demands and is conceptualized as an aspect of executive function. The dopamine system has been implicated in cognitive flexibility; however, a direct, that is, neurochemical, link to cognitive flexibility has not been shown yet. The aim of this study was, therefore, to investigate how cognitive flexibility is mediated by dopaminergic signaling in the ventromedial prefrontal cortex (vmPFC). <b>Methods:</b> Eighteen participants were measured in a PET study with 174 ± 12 MBq of the D_2/3 receptor ligand [¹⁸F]fallypride in a block design with 2 parts. While participants processed 2 tasks sequentially without rule switching on a computer screen in the first part of the PET scan, they had to flexibly switch between the 2 task rules after 100 min after injection in the second part. Dopamine release (γ) was quantified using the linearized simplified reference region model contrasting the 2 task blocks (switching vs. no-switching/baseline). <b>Results:</b> The statistical analysis of the parametric γ-images showed that the increased cognitive demand during task switching induced a displacement of the D_2/3 receptor ligand [¹⁸F]fallypride in the vmPFC (maximum T value = 13.8; cluster size: 528 voxels; familywise error rate-corrected <i>P</i> < 0.001; mean γ = 0.022 ± 0.006 min^-1). Furthermore, a correlation between behavioral switch costs and vmPFC [¹⁸F]fallypride displacement suggested that participants showing greater dopamine release were more efficient in task switching. <b>Conclusion:</b> To our knowledge, this is the first experimental PET study to show direct involvement of dopamine in the vmPFC in a task-switching paradigm, confirming model assumptions about the neurochemical basis of cognitive flexibility.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"405-409"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070518","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":"China's Innovations in Nuclear Medicine: Global Insights into Clinical Advancements and Impact.","authors":"Xun Wang, Yifan Dong, Shuo Zhang","doi":"10.2967/jnumed.124.269185","DOIUrl":"10.2967/jnumed.124.269185","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"351"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070509","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":"MIRD Pamphlet No. 32: A MIRD Recovery Coefficient Model for Resolution Characterization and Shape-Specific Partial-Volume Correction.","authors":"Harry Marquis, C Ross Schmidtlein, Robin de Nijs, Pablo Mínguez Gabiña, Johan Gustafsson, Gunjan Kayal, Juan C Ocampo Ramos, Lukas M Carter, Dale L Bailey, Adam L Kesner","doi":"10.2967/jnumed.124.268520","DOIUrl":"10.2967/jnumed.124.268520","url":null,"abstract":"<p><p>Accurate quantification in emission tomography is essential for internal radiopharmaceutical therapy dosimetry. Mean activity concentration measurements in objects with diameters less than 10 times the full width at half maximum of the imaging system's spatial resolution are significantly affected (>10%) by the partial-volume effect. This study develops a framework for PET and SPECT spatial resolution characterization and proposes 2 MIRD recovery coefficient models-a geometric mean approximation (RECOVER-GM) and an empirical model (RECOVER-EM)-that provide shape-specific partial-volume correction (PVC). The models were validated using simulations and phantom experiments, with a comparative PVC test on ellipsoidal phantoms demonstrating that the RECOVER models significantly reduced error in activity quantification by factors of approximately 1.3-5.7 compared with conventional sphere-based corrections. The proposed recovery coefficient models and PVC methodology provide a robust framework for improved region-based PVC, including corrections for nonspherical tumor volumes. This work is part of the ongoing MIRDsoft.org project that aims to enhance accessibility to advanced dosimetry tools for improved disease characterization, treatment planning, and radiopharmaceutical therapy dosimetry.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"457-465"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosimetry of [¹⁷⁷Lu]Lu-DOTATATE in Patients with Advanced Midgut Neuroendocrine Tumors: Results from a Substudy of the Phase III NETTER-1 Trial.","authors":"Lisa Bodei, Marta Cremonesi, Mahila Ferrari, Erik S Mittra, Harshad R Kulkarni, Christophe M Deroose, Rajaventhan Srirajaskanthan, John Ramage, Chiara Maria Grana, Francesca Botta, Matthias M Weber, Matthias Miederer, Ryan Reddy, Daniela Chicco, Maurizio F Mariani, Arnaud Demange, Jack L Erion, Germo Gericke, Eric Krenning","doi":"10.2967/jnumed.124.268903","DOIUrl":"10.2967/jnumed.124.268903","url":null,"abstract":"<p><p>This substudy of the phase III NETTER-1 trial evaluated [¹⁷⁷Lu]Lu-DOTATATE (hereafter ¹⁷⁷Lu-DOTATATE) for advanced midgut neuroendocrine tumors and aimed to assess dosimetry of a standard 4-cycle protocol and any potential relationship to toxicity. Change in tumor size by absorbed dose was an exploratory endpoint. <b>Methods:</b> Patients with locally advanced or metastatic, well-differentiated, midgut neuroendocrine tumors were enrolled in this substudy between August 2013 and January 2016. Patients were scheduled to receive 4 infusions of 7.4 GBq of ¹⁷⁷Lu-DOTATATE for a cumulative injected activity of 29.6 GBq. After a ¹⁷⁷Lu-DOTATATE infusion, whole-body planar images (4-6 time points for up to 7 d) and SPECT/CT images (at 24 and/or 48 h) were acquired, and absorbed and time-integrated activity coefficients were calculated to derive dosimetry. Blood and urine samples were used to determine the blood clearance and activity elimination rate. Tumor absorbed dose was derived using a sphere model, interpolating ¹⁷⁷Lu dose factors on the basis of each lesion mass. Tumor size was assessed by measuring the longest and perpendicular dimensions on CT at measured time points. <b>Results:</b> Dosimetric assessments were evaluated in 20 patients. Organ dosimetry showed substantial interpatient variability. The predicted mean cumulative absorbed doses to kidneys and bone marrow were 19.4 (SD, 8.7) and 1.0 (SD, 0.8) Gy, respectively. Three patients had kidney doses between 28 and 33 Gy; 2 had grade 1 increased serum creatinine, and 1 showed no evidence of renal toxicity (up to 5 y of follow-up). Hematologic toxicity was primarily mild or moderate (grade 1-2) with no increase over time or association with cumulative absorbed dose. Tumor kinetics in 65 lesions demonstrated stable activity over time. Inter- and intrapatient variability was observed, and the median cumulative absorbed dose was 134 Gy (range, 7-2,218 Gy). Acknowledging the limitations of the imaging methods used and tumor volume assessments, we found no correlation between the best tumor size reduction and the absorbed dose, though most tumors (90%) shrank over the 72-wk study period. <b>Conclusion:</b> The dosimetry data support the findings that the standard treatment regimen with ¹⁷⁷Lu-DOTATATE that includes personalized adjustments according to acute toxicity assessments is well tolerated and manageable.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"449-456"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of ¹⁷⁷Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma.","authors":"Cameron N Johnstone, Laura D Osellame, Zhipeng Cao, Alexander F McDonald, Angela Rigopoulos, Ingrid J G Burvenich, Christian W Wichmann, Nancy Guo, Alesia N Ivashkevich, Michael P Wheatcroft, Edwin B Yan, Astrid Zimmermann, Frank T Zenke, Christian Sirrenberg, Fiona E Scott, Andrew M Scott","doi":"10.2967/jnumed.124.268695","DOIUrl":"10.2967/jnumed.124.268695","url":null,"abstract":"<p><p>Novel radiation sensitizers, including inhibitors targeting DNA damage response, have been developed to enhance the efficacy of anticancer treatments that induce DNA damage in cancer cells. Peposertib, a potent, selective, and orally administered inhibitor of DNA-dependent protein kinase, impedes the nonhomologous end-joining mechanism for DNA double-strand break (DSB) repair. We investigated radioimmunotherapy alone or with peposertib in preclinical models of renal cell carcinoma (RCC) or prostate cancer. <b>Methods:</b> ¹⁷⁷Lu-DOTA-girentuximab (targeting carbonic anhydrase IX) or ¹⁷⁷Lu-DOTA-rosopatamab (targeting prostate-specific membrane antigen) was used to deliver β-radiation to tumors via a single intravenous dose (3 or 6 MBq) in mice bearing SK-RC-52 RCC or LNCaP prostate cancer xenografts, respectively. Peposertib (50 mg/kg daily for 14 d) was administered via oral gavage. Biodistribution and in vivo imaging of ¹⁷⁷Lu-based radioimmunotherapy were performed for both preclinical models. Tumor growth and body weight were monitored until the endpoint. Assessment of DNA damage was performed by measuring DSBs through analysis of γH2AX foci formation in tumor sections. <b>Results:</b> Ex vivo biodistribution and in vivo SPECT/MRI revealed excellent tumor uptake of each radiopharmaceutical. Mouse body weight was stable in all treatment arms. Peposertib alone did not show a significant antitumor effect. The addition of peposertib to ¹⁷⁷Lu-DOTA-girentuximab showed enhanced antitumor efficacy compared with ¹⁷⁷Lu-DOTA-girentuximab alone in the SK-RC-52 animal model, with a 4 of 4 complete response rate in the ¹⁷⁷Lu-DOTA-girentuximab (6 MBq) plus peposertib arm. Peposertib combined with low-dose ¹⁷⁷Lu-DOTA-girentuximab (3 MBq) demonstrated antitumor activity comparable to ¹⁷⁷Lu-DOTA-girentuximab (6 MBq) monotherapy. In the LNCaP prostate cancer model, the combination of ¹⁷⁷Lu-DOTA-rosopatamab (6 MBq) and peposertib achieved a 3 of 4 complete response rate. Increased DSBs were observed with the addition of peposertib to ¹⁷⁷Lu-based radioimmunotherapy. <b>Conclusion:</b> The combination of peposertib with ¹⁷⁷Lu-based radioimmunotherapy was well tolerated in preclinical models of RCC and prostate cancer. Our findings suggest a synergistic effect between peposertib and ¹⁷⁷Lu-based radioimmunotherapy, wherein peposertib enhanced the efficacy of radioimmunotherapy. This synergy indicates the potential to reduce the necessary dose of radioimmunotherapy for effective cancer treatment.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"385-390"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070515","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":"[¹⁸F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [¹⁵O]Water.","authors":"Jessie Fanglu Fu, Meher R Juttukonda, Arun Garimella, Andrew N Salvatore, Cristina Lois, Anthony Ranasinghe, Nikos Efthimiou, Hasan Sari, William Aye, Nicolas J Guehl, Georges El Fakhri, Keith A Johnson, Bradford C Dickerson, David Izquierdo-Garcia, Ciprian Catana, Julie C Price","doi":"10.2967/jnumed.124.268701","DOIUrl":"10.2967/jnumed.124.268701","url":null,"abstract":"&lt;p&gt;&lt;p&gt;[&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 PET (where MK-6240 is 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is used to assess in vivo tau deposition across the Alzheimer disease (AD) spectrum. We aimed to quantify the associations and bias of early-frame [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 PET as surrogates for cerebral perfusion against gold standard [&lt;sup&gt;15&lt;/sup&gt;O]water PET and the potential impact of cerebral perfusion on [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 tau quantification across aging and the AD spectrum. &lt;b&gt;Methods:&lt;/b&gt; Fourteen cognitively normal (CN, 4 young CN and 10 old CN) and 3 AD participants underwent dynamic [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 PET, with 9 undergoing arterial sampling. A subset (&lt;i&gt;n&lt;/i&gt; = 11) underwent [&lt;sup&gt;15&lt;/sup&gt;O]water PET. [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 perfusion indices were estimated as radiotracer delivery indices &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; (using 2-tissue-compartment models), and relative perfusion indices were estimated as R&lt;sub&gt;1&lt;/sub&gt; (using compartmental and reference tissue models, cerebellar gray matter reference region) and early-frame SUV ratio (0-3 min). [&lt;sup&gt;15&lt;/sup&gt;O]water &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; and R&lt;sub&gt;1&lt;/sub&gt; were estimated using 1-tissue-compartment models). [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 tau burden was estimated using distribution volume ratio and SUV ratio at 90-110 min. Spearman correlations, linear mixed-effect models, and Bland-Altman analyses examined relationships between [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 perfusion indices against [&lt;sup&gt;15&lt;/sup&gt;O]water and between estimates of perfusion and tau burden in tau-relevant regions. The impact of partial-volume correction was examined. &lt;b&gt;Results:&lt;/b&gt; Significant correlations were observed between [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; and [&lt;sup&gt;15&lt;/sup&gt;O]water &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; (ρ = 0.57); However, [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; underestimated [&lt;sup&gt;15&lt;/sup&gt;O]water &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; by up to 50%, with a strong negative proportional bias. Significant correlations were observed between [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 relative perfusion and [&lt;sup&gt;15&lt;/sup&gt;O]water R&lt;sub&gt;1&lt;/sub&gt; (ρ &gt; 0.84), with minimal bias. In 2 AD participants, significant correlations were observed between perfusion and [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 retention. Applying partial-volume correction did not significantly impact the correlations or improve the underestimations in [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 &lt;i&gt;K&lt;/i&gt; &lt;sub&gt;1&lt;/sub&gt; &lt;b&gt;Conclusion:&lt;/b&gt; Using head-to-head [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 and [&lt;sup&gt;15&lt;/sup&gt;O]water data, we showed that [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 exhibited a relatively low extraction fraction, leading to underestimation of cerebral perfusion. Our results provide further support for [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 R&lt;sub&gt;1&lt;/sub&gt; as a reliable estimate of relative cerebral perfusion, with strong associations and minimal bias compared with [&lt;sup&gt;15&lt;/sup&gt;O]water. In addition, lower perfusion may be associated with higher [&lt;sup&gt;18&lt;/sup&gt;F]MK-6240 retention in tau-relevant regions in AD. These findings further support the ","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"410-417"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}