The Journal of Nuclear Medicine最新文献

{"title":"Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT","authors":"Hudson Alakonya, Sofia Koustoulidou, Samantha L. Hopkins, Mathew Veal, Javier Ajenjo, Deborah Sneddon, Gemma Dias, Michael Mosley, Julia Baguña Torres, Francesca Amoroso, Amanda Anderson, Alison H. Banham, Bart Cornelissen","doi":"10.2967/jnumed.124.267736","DOIUrl":"https://doi.org/10.2967/jnumed.124.267736","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.267736absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174575","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":"The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for 161Tb Compared with 177Lu with a Higher Dose Response for [161Tb]Tb-DOTA-LM3 Than for [161Tb]Tb-DOTATATE","authors":"Kaat Spoormans, Lara Struelens, Koen Vermeulen, Marijke De Saint-Hubert, Michel Koole, Melissa Crabbé","doi":"10.2967/jnumed.124.267873","DOIUrl":"https://doi.org/10.2967/jnumed.124.267873","url":null,"abstract":"&lt;p&gt;Preclinical data have shown that &lt;sup&gt;161&lt;/sup&gt;Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their &lt;sup&gt;177&lt;/sup&gt;Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. &lt;strong&gt;Methods:&lt;/strong&gt; CA20948 cell survival was assessed after treatment with [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb- and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTATATE (agonist) and with [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb- and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate &lt;em&gt;S&lt;/em&gt; values for each type of particle emission (Auger/internal conversion [IC] electrons and β&lt;sup&gt;−&lt;/sup&gt; particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. &lt;strong&gt;Results:&lt;/strong&gt; Although the radiopeptide uptake was independent of the radionuclide, [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTATATE and [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their &lt;sup&gt;177&lt;/sup&gt;Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by &lt;sup&gt;161&lt;/sup&gt;Tb. When activity concentrations were considered, both [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTATATE and [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with &lt;sup&gt;177&lt;/sup&gt;Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb- and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTATATE. [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. &lt;strong&gt;Conclusion:&lt;/strong&gt; The IC, rather than Auger, electrons emitted by &lt;sup&gt;161&lt;/sup&gt;Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTATATE and [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 than for the &lt;sup&gt;177&lt;/sup&gt;Lu-labeled analogs. In contrast, [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTATATE showed no higher dose response than [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTATATE, whereas for [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [&lt;sup&gt;161&lt;/sup&gt;Tb]Tb","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100847","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":"Association Between CA 15-3 and 18F-FDG PET/CT Findings in Recurrent Breast Cancer Patients at a Tertiary Referral Hospital in Kenya","authors":"Margaret M. Mwania, Samuel Nguku Gitau, Jasmit Shah, Khalid Makhdomi","doi":"10.2967/jnumed.124.267851","DOIUrl":"https://doi.org/10.2967/jnumed.124.267851","url":null,"abstract":"<p>The tumor marker cancer antigen 15-3 (CA 15-3) is that most commonly used to monitor metastatic breast cancer during active therapy and surveillance for disease recurrence after treatment. The association of CA 15-3 and ¹⁸F-FDG PET/CT findings can be considered complementary, since any significant rise may indicate the presence of disease and imaging is able to map the tumor sites. Although current guidelines do not recommend the routine performance of CA 15-3 in asymptomatic patients being followed up after definitive breast cancer treatment, most oncologists perform serial assessment of the tumor markers as part of routine follow-up of patients. The aim of this study was to evaluate the correlation between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings in patients with recurrent breast cancer. <strong>Methods:</strong> This was a cross-sectional study with data collected retrospectively. Patients being evaluated for breast cancer recurrence with ¹⁸F-FDG PET/CT imaging and CA 15-3 level were included. Evaluation of the association between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings was then done. <strong>Results:</strong> In total, 154 cases were included in this study; 62 patients had recurrence (positive) on the ¹⁸F-FDG PET/CT scans, whereas 92 patients had normal (negative) findings on follow-up ¹⁸F-FDG PET/CT scans. There was an association between CA 15-3 levels and the presence or absence of recurrence on ¹⁸F-FDG PET/CT scans, with 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT and 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT as well as a correlation with the burden of metastases. Most patients with disease recurrence on ¹⁸F-FDG PET/CT, however, had normal CA 15-3 levels. <strong>Conclusion:</strong> Higher CA 15-3 levels correlate with breast cancer recurrence on ¹⁸F-FDG PET/CT as well as with burden of metastasis. Notably, CA 15-3 levels within the reference range do not exclude breast cancer disease recurrence since more than half of patients with recurrence had normal CA 15-3 levels. ¹⁸F-FDG PET/CT should therefore be considered in patients with suspected breast cancer recurrence but normal CA 15-3 levels.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100750","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":"Improving 18F-FDG PET Quantification Through a Spatial Normalization Method","authors":"Daewoon Kim, Seung Kwan Kang, Seong A. Shin, Hongyoon Choi, Jae Sung Lee","doi":"10.2967/jnumed.123.267360","DOIUrl":"https://doi.org/10.2967/jnumed.123.267360","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.123.267360absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100753","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":"Prognostic Value of 18F-FDG PET/CT Assessment After Radiotherapy of Squamous Cell Carcinoma of the Anus in Patients from the National Multicentric Cohort FFCD-ANABASE","authors":"Virginie Combet-Curt, Chloé Buchalet, Karine Le Malicot, Claire Lemanski, Emmanuel Deshayes, Nathalie Bonichon-Lamichhane, Astrid Lièvre, Florence Huguet, Ghoufrane Tlili, Véronique Vendrely","doi":"10.2967/jnumed.124.267626","DOIUrl":"https://doi.org/10.2967/jnumed.124.267626","url":null,"abstract":"<p>This study aimed to evaluate the prognostic value of ¹⁸F-FDG PET/CT qualitative assessment in terms of recurrence-free survival (RFS), colostomy-free survival (CFS), and overall survival (OS) after radiation therapy (RT) of squamous cell carcinoma of the anus (SCCA). Secondary objectives were to evaluate the prognostic value of baseline and posttherapeutic quantitative ¹⁸F-FDG PET/CT parameters in terms of RFS, CFS, and OS. <strong>Methods:</strong> We included all consecutive patients from the French multicentric cohort FFCD-ANABASE who had undergone ¹⁸F-FDG PET/CT at baseline and 4–6 mo after RT or chemoradiotherapy for a localized SCCA. Qualitative assessments separated patients with complete metabolic response (CMR) and non-CMR. Quantitative parameters were measured on baseline and posttreatment ¹⁸F-FDG PET/CT. RFS, CFS, and OS were analyzed using the Kaplan–Meier method. Associations among qualitative assessments, quantitative parameters, and RFS, CFS, and OS were analyzed using univariate and multivariate Cox regression. <strong>Results:</strong> Among 1,015 patients treated between January 2015 and April 2020, 388 patients (300 women and 88 men) from 36 centers had undergone ¹⁸F-FDG PET/CT at diagnosis and after treatment. The median age was 65 y (range, 32–90 y); 147 patients (37.9%) had an early-stage tumor and 241 patients (62.1%) had a locally advanced-stage tumor; 59 patients (15.2%) received RT, and 329 (84.8%) received chemoradiotherapy. The median follow-up was 35.5 mo (95% CI, 32.8–36.6 mo). Patients with CMR had better 3-y RFS, CFS, and OS, at 84.2% (95% CI, 77.8%–88.9%), 84.7% (95% CI, 77.2%–89.3%), and 88.6% (95% CI, 82.5%–92.7%), respectively, than did non-CMR patients, at 42.1% (95% CI, 33.4%–50.6%), 47.9% (95% CI, 38.1%–56.8%), and 63.5 (95% CI, 53.2%–72.1%), respectively (<em>P</em> &lt; 0.0001). Quantitative parameters were available for 154 patients from 3 centers. The following parameters were statistically significantly associated with 3-y RFS: baseline SUV_max (primitive tumor [T]) (hazard ratio [HR], 1.05 [95% CI, 1.01–1.1; <em>P</em> = 0.018]), SUV_peak (T) (HR, 1.09 [95% CI, 1.02–1.15; <em>P</em> = 0.007]), MTV 41% (T) (HR, 1.02 [95% CI, 1–1.03; <em>P</em> = 0.023]), MTV 41% (lymph node [N]) (HR, 1.06 [95% CI, 1.03–1.1; <em>P</em> &lt; 0.001]), MTV 41% (T + N) (HR, 1.02 [95% CI, 1–1.03; <em>P</em> = 0.005]), and posttreatment SUV_max (HR, 1.21 [95% CI, 1.09–1.34; <em>P</em> &lt; 0.001]). <strong>Conclusion:</strong> Treatment response assessed by ¹⁸F-FDG PET/CT after RT for SCCA has a significant prognostic value.¹⁸F-FDG PET/CT could be useful for adapting follow-up, especially for patients with locally advanced-stage tumors. Quantitative parameters could permit identification of patients with a worse prognosis but should be evaluated in further trials.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462405","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":"Impact of the Reference Multiple-Time-Point Dosimetry Protocol on the Validity of Single-Time-Point Dosimetry for [177Lu]Lu-PSMA-I&T Therapy","authors":"Sandra Resch, Sibylle I. Ziegler, Gabriel Sheikh, Lena M. Unterrainer, Mathias J. Zacherl, Peter Bartenstein, Guido Böning, Julia Brosch-Lenz, Astrid Delker","doi":"10.2967/jnumed.123.266871","DOIUrl":"https://doi.org/10.2967/jnumed.123.266871","url":null,"abstract":"<p>Internal dosimetry supports safe and effective patient management during radionuclide therapy. Yet, it is associated with high clinical workload, costs, and patient burden, as patient scans at multiple time points (MTPs) must be acquired. Dosimetry based on imaging at a single time point (STP) has continuously gained popularity. However, MTP protocols, used as a reference to judge the validity of STP dosimetry, differ depending on local requirements and deviate from the unknown patient-specific ground truth pharmacokinetics. The aim of this study was to compare the error and optimum time point for different STP approaches using different reference MTP protocols. <strong>Methods:</strong> Whole-body SPECT/CT scans of 7 patients (7.4–8.9 GBq of [¹⁷⁷Lu]Lu-PSMA-I&amp;T) were scheduled at 24, 48, 72, and 168 h after injection. Sixty lesions, 14 kidneys, and 10 submandibular glands were delineated in the SPECT/CT data. Two curve models, that is, a mono- and a biexponential model, were fitted to the MTP data, in accordance with goodness-of-fit analysis (coefficients of variation, sum of squared errors). Three population-based STP approaches were compared: one method published by Hänscheid et al., one by Jackson et al., and one using population-based effective half-lives in the mono- or biexponential curve models. Percentage differences between STP and MTP dosimetry were evaluated. <strong>Results:</strong> Goodness-of-fit parameters show that a monoexponential function and a biexponential function with shared population-based parameters and physical tail are reasonable reference models. When comparing both reference models, we observed maximum differences of −44%, −19%, and −28% in the estimated absorbed doses for lesions, kidneys, and salivary glands, respectively. STP dosimetry with an average deviation of less than 10% from MTP dosimetry may be feasible; however, this deviation and the optimum imaging time point showed a dependence on the chosen reference protocol. <strong>Conclusion:</strong> STP dosimetry for [¹⁷⁷Lu]Lu-PSMA therapy is promising to boost the integration of dosimetry into clinical routine. According to our patient cohort, 48 h after injection may be regarded as a compromise for STP dosimetry for lesions and at-risk organs. The results from this analysis show that a common gold standard for dosimetry is desirable to allow for reliable and comparable STP dosimetry.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462424","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":"Prostate-Specific Membrane Antigen–Targeted Imaging and Its Correlation with HOXB13 Expression","authors":"Duminduni Hewa Angappulige, Nimrod S. Barashi, Nicholas Pickersgill, Cody Weimholt, Jingqin Luo, Ghazal Shadmani, Ziad Tarcha, Sampanna Rayamajhi, Nupam P. Mahajan, Gerald L. Andriole, Barry A. Siegel, Eric H. Kim, Kiran Mahajan","doi":"10.2967/jnumed.123.267301","DOIUrl":"https://doi.org/10.2967/jnumed.123.267301","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.123.267301absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462518","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 and Efficacy of Radiosynoviorthesis: A Prospective Canadian Multicenter Study","authors":"Mélanie Desaulniers, Michel Paquette, Stéphanie Dubreuil, Helena Senta, Éric Lavallée, J. Carter Thorne, Éric Turcotte","doi":"10.2967/jnumed.123.267297","DOIUrl":"https://doi.org/10.2967/jnumed.123.267297","url":null,"abstract":"<p>Radiosynoviorthesis is approved in several European countries and the United States to treat refractory synovitis in many inflammatory joint diseases, such as rheumatoid arthritis, spondyloarthropathies, and other arthritic joint diseases. No radiopharmaceuticals for radiosynoviorthesis are currently approved in Canada. The aim of this Health Canada–approved trial was to demonstrate the safety and efficacy of radiosynoviorthesis. <strong>Methods:</strong> Between July 2012 and November 2017, we conducted a multicenter, prospective, interventional Canadian trial. Patients (<em>n</em> = 360) with synovitis refractory to standard treatments after failing 2 intraarticular glucocorticoid injections were included. They were followed up at 3, 6, and 12 mo. Outcome measures included adverse events (AEs) and clinical signs of synovitis (pain, swelling, and joint effusion) measured with the Health Assessment Questionnaire Disability Index, the Disease Activity Score, and the Visual Analog Scale. <strong>Results:</strong> In total, 392 joints were treated, including those reinjected after 6 mo (<em>n</em> = 34). Of these, 83.4% (327/392) were injected with [⁹⁰Y]Y-citrate for the knees and 9.9% (39/392) with [¹⁸⁶Re]Re-sulfide for medium-sized joints. Of the joints treated, 82.7% (324/392) were knees. Fifty-five AEs, most of them of mild grade, occurred and resolved without sequelae and were not life-threatening. The incidence of radiosynoviorthesis-related AEs was 9.4% (34/360). The proportion of patients showing an improvement in synovitis symptoms after radiosynoviorthesis was significant at 3 mo and was maintained up to 12 mo (<em>P</em> &lt; 0.001). <strong>Conclusion:</strong> This study confirmed the safety of radiosynoviorthesis in the treatment of patients with synovitis refractory to standard treatments. There is evidence of sustained clinical efficacy at 12 mo, suggesting that radiosynoviorthesis is an effective treatment for improving synovitis symptoms.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953718","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":"Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease","authors":"Pedram Heidari, Arvin Haj-Mirzaian, Suma Prabhu, Bahar Ataeinia, Shadi A. Esfahani, Umar Mahmood","doi":"10.2967/jnumed.123.267344","DOIUrl":"https://doi.org/10.2967/jnumed.123.267344","url":null,"abstract":"<p>Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with ⁶⁸Ga-NOTA-GZP (where GZP is β-Ala–Gly–Gly–Ile–Glu–Phe–Asp–CHO) to detect early intestinal inflammation in murine models of colitis. <strong>Methods:</strong> Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10^−/− mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti–tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with ⁶⁸Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. <strong>Results:</strong> Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD (<em>P</em> = 0.032).⁶⁸Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10^−/− mice with DSS-induced colitis compared with vehicle-treated IL-10^−/− mice (SUV_mean, 0.75 vs. 0.24; <em>P</em> &lt; 0.001) and both vehicle- and DSS-treated wild-type mice (SUV_mean, 0.26 and 0.37; <em>P</em> &lt; 0.001). In the IL-10^−/− DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor–α (SUV_mean, 0.32; <em>P</em> &lt; 0.001). There was a 4-fold increase in colonic uptake of ⁶⁸Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUV_mean, 0.23 vs. 0.08; <em>P</em> = 0.001). <strong>Conclusion:</strong> GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953755","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":"Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment","authors":"Yifei Ma, Jiling Zeng, Fadian Ding, Yiwei Xu, Youlong Wang, Guanqing Zhong, Nianqi Liu, Yanqi Wang, Yiming Li, Shuqin Chen, Xiaolong Wei, Pengfei Zhu, Guangmin Jian, Yu Si Niu, Guangzhen Fu, Cantong Liu, Guiqiang Li, Xiaotong Zhou, Ao Zhang, Shangeng Weng","doi":"10.2967/jnumed.123.267025","DOIUrl":"https://doi.org/10.2967/jnumed.123.267025","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.123.267025absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821093","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}