The Journal of Nuclear Medicine最新文献

{"title":"Artificial Intelligence–Enhanced Perfusion Scoring Improves the Diagnostic Accuracy of Myocardial Perfusion Imaging","authors":"Robert J.H. Miller, Paul Kavanagh, Mark Lemley, Joanna X. Liang, Tali Sharir, Andrew J. Einstein, Mathews B. Fish, Terrence D. Ruddy, Philipp A. Kaufmann, Albert J. Sinusas, Edward J. Miller, Timothy M. Bateman, Sharmila Dorbala, Marcelo Di Carli, Sean Hayes, John Friedman, Daniel S. Berman, Damini Dey, Piotr J. Slomka","doi":"10.2967/jnumed.124.268079","DOIUrl":"https://doi.org/10.2967/jnumed.124.268079","url":null,"abstract":"<p>We previously demonstrated that a deep learning (DL) model of myocardial perfusion SPECT imaging improved accuracy for detection of obstructive coronary artery disease (CAD). We aimed to improve the clinical translatability of this artificial intelligence (AI) approach using the results to derive enhanced total perfusion deficit (TPD) and 17-segment summed scores. <strong>Methods:</strong> We used a cohort of patients undergoing myocardial perfusion imaging within 180 d of invasive coronary angiography. Obstructive CAD was defined as any stenosis of at least 70% or at least 50% in the left main coronary artery. We used per-vessel DL predictions to modulate polar map pixel scores. These transformed polar maps were then used to derive TPD-DL and summed stress score–DL. We compared diagnostic performance using area under the receiver operating characteristic curve (AUC). <strong>Results:</strong> In the 555 patients held out for testing, the median age was 65 y (interquartile range, 57–73 y), and 381 (69%) were male. Obstructive CAD was present in 329 (59%) patients. The prediction performance for obstructive CAD of stress TPD-DL (AUC, 0.837; 95% CI, 0.804–0.870) was higher than AI prediction alone (AUC, 0.795; 95% CI, 0.758–0.831; <em>P</em> = 0.005) and traditional stress TPD (AUC, 0.737; 95% CI, 0.696–0.778; <em>P</em> &lt; 0.001). Summed stress score–DL had the second highest prediction performance (AUC, 0.822; 95% CI, 0.788–0.857) and higher AUC than traditional quantitative summed stress score (AUC, 0.728; 95% CI, 0.686–0.769; <em>P</em> &lt; 0.001). At a threshold of 5%, the sensitivity and specificity of TPD rose from 72% to 79% and from 62% to 70%, respectively. <strong>Conclusion:</strong> Integrating AI predictions with traditional quantitative approaches leads to a simplified AI approach, presenting clinicians with familiar measures but operating with higher accuracy than traditional quantitative scoring. This approach may facilitate integration of new AI methods into clinical practice.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462477","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":"225Ac/89Zr-Labeled N4MU01 Radioimmunoconjugates as Theranostics Against Nectin-4–Positive Triple-Negative Breast Cancer","authors":"Hanan Babeker, Fabrice Ngoh Njotu, Jessica Pougoue Ketchemen, Alissar Monzer, Anjong Florence Tikum, Alireza Doroudi, Emmanuel Nwangele, Maruti Uppalapati, Humphrey Fonge","doi":"10.2967/jnumed.124.268387","DOIUrl":"https://doi.org/10.2967/jnumed.124.268387","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.268387absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"209 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462479","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":"Clinical Trial Protocol for LuCAB: A Phase I–II Trial Evaluating Cabazitaxel in Combination with [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer","authors":"Louise Kostos, James P. Buteau, Grace Kong, Ben Tran, Mohammad B. Haskali, Michael Fahey, Megan Crumbaker, Louise Emmett, Michael S. Hofman, Arun A. Azad","doi":"10.2967/jnumed.124.269252","DOIUrl":"https://doi.org/10.2967/jnumed.124.269252","url":null,"abstract":"<p>[¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA)–617 is a standard treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and an androgen receptor pathway inhibitor. However, for many, responses are short and progression is inevitable. Contributing factors to treatment resistance include molecular heterogeneity with variable PSMA expression, micrometastases that may not absorb sufficient radiation from ¹⁷⁷Lu to result in cell death, and inherent or acquired radioresistance because of genomic alterations or the tumor microenvironment. Cabazitaxel is a radiosensitizer and may treat PSMA-negative disease that would otherwise evade targeting by [¹⁷⁷Lu]Lu-PSMA-617. We hypothesize that the combination of [¹⁷⁷Lu]Lu-PSMA-617 and cabazitaxel will be synergistic with an acceptable safety profile. <strong>Methods:</strong> This investigator-initiated phase I–II trial aims to evaluate the safety, tolerability, and preliminary efficacy of cabazitaxel and [¹⁷⁷Lu]Lu-PSMA-617 in combination. Up to 38 patients with mCRPC will receive up to 6 doses of [¹⁷⁷Lu]Lu-PSMA-617 administered intravenously every 6 wk at a fixed dose of 7.4 GBq. Cabazitaxel will be administered concurrently (dose range, 12.5–20 mg/m²) on day 2 and day 23 of each 6-wk cycle, with dose escalation determined using a traditional 3 + 3 design to establish the maximum tolerated or administered dose. Key eligibility criteria include a diagnosis of progressive mCRPC with PSMA-positive disease on PSMA PET/CT (SUV_max ≥ 15) and no sites of discordance on [¹⁸F]F-FDG PET/CT. Patients must have received prior docetaxel and an androgen receptor pathway inhibitor, have adequate bone marrow and organ function, and have an Eastern Cooperative Oncology Group performance status of 0 or 1. The primary objective is to assess for dose-limiting toxicities and determine the recommended phase II dose of cabazitaxel and [¹⁷⁷Lu]Lu-PSMA-617 in combination. Secondary objectives include further safety evaluation through the measurement of the frequency and severity of adverse events, assessment of efficacy, and evaluation of changes in pain and health-related quality of life over the first 12 mo from treatment commencement. Plasma will be collected at baseline, during treatment, and at disease progression for circulating tumor DNA analysis, which will be correlated with clinical outcomes to identify potential biomarkers of treatment response or resistance. <strong>Conclusion:</strong> Enrollment commenced in August 2022, with anticipated completion in 2025.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462481","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":"Theranostics for Neuroblastoma: Making Molecular Radiotherapy Work Better","authors":"Peter J. Gawne, Helen E. Bryant, Steven G. DuBois, Sally L. George, Juliet Gray, Leona Knox, Kyle B. Matchett, Connie Peet, Katherine A. Vallis, Hugh J. Wallace, Simon Wan, Mark N. Gaze","doi":"10.2967/jnumed.124.269121","DOIUrl":"https://doi.org/10.2967/jnumed.124.269121","url":null,"abstract":"<p>Despite improvements in neuroblastoma treatment, survival figures lag behind those of many other childhood malignancies. New treatments, and better use of existing treatments, are essential to reduce mortality. Neuroblastoma expresses several molecular targets for radionuclide imaging and therapy, of which the most widely exploited is the norepinephrine transporter. [¹²³I]metaiodobenzylguanidine (MIBG) imaging and [¹³¹I]MIBG treatment, which target this physiologic pathway, have been in clinical practice for 40 y. Although therapy outcomes have been favorable, [¹³¹I]MIBG use has not yet been optimized. Somatostatin receptors and the disialoganglioside are alternative targets, but their use remains experimental. The charity Children&rsquo;s Cancer Research Fund organized a workshop bringing together a broad range of scientists including radiochemists, radiobiologists, radiation physicists, clinical researchers including pediatric oncologists and nuclear medicine physicians, and patient advocates from the United Kingdom, United States, and continental Europe to share their experiences with molecular imaging and radiotherapy of neuroblastoma and discuss potential ways of improving treatment outcomes and access. These include development of alternative vectors targeting somatostatin receptors and disialoganglioside, isotopes such as &alpha;-particle and Auger electron emitters with different radiation characteristics, and combinations with external-beam radiotherapy, immunotherapy, and DNA damage repair inhibitors. Barriers to progress discussed included the unpredictable radioisotope supply, production of novel radiopharmaceuticals, lack of data regarding which are the best combination therapies, and insufficient clinical facilities. The aim was to stimulate the development and assessment of more effective treatments.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462483","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":"Evaluation of Surgical Margins with Intraoperative PSMA PET/CT and Their Prognostic Value in Radical Prostatectomy","authors":"Alexandros Moraitis, Theresa Kahl, Jens Kandziora, Walter Jentzen, David Kersting, Lukas Püllen, Henning Reis, Jens Köllermann, Claudia Kesch, Ulrich Krafft, Boris A. Hadaschik, Habib Zaidi, Ken Herrmann, Francesco Barbato, Wolfgang P. Fendler, Christopher Darr, Pedro Fragoso Costa","doi":"10.2967/jnumed.124.268719","DOIUrl":"https://doi.org/10.2967/jnumed.124.268719","url":null,"abstract":"<p>Detection of positive resection margins in surgical procedures of high-risk prostate cancer is key for minimizing the risk of recurrence. This study aimed at evaluating the accuracy of functional tumor-volume segmentation in intraoperative ex vivo PET/CT for margin assessment in prostate cancer patients undergoing radical prostatectomy. <strong>Methods:</strong> Seven high-risk prostate cancer patients received [¹⁸F]PSMA-1007 before radical prostatectomy. After removal of the prostate gland, ex vivo imaging on the AURA 10 PET/CT system was performed, and functional tumor volume was segmented using 4 semiautomatic segmentation methods. Resection margins and volumes were compared with histopathology. Additionally, a supportive phantom study was conducted to assess segmentation accuracy at low radiopharmaceutical activity. <strong>Results:</strong> Clinically, 18 lesions were analyzed in intraoperative PET/CT. Sensitivity, specificity, and positive and negative predictive values of margin detection were 83%, 100%, 100%, and 92%, respectively, using an iterative thresholding method. In 1 patient, a biochemical recurrence was observed within 1 y of prostate-specific antigen follow-up, and 1 patient underwent adjuvant radiotherapy. The remaining 5 patients were still undergoing prostate-specific antigen follow-up with no evidence of biochemical recurrence. On the basis of a phantom-deduced minimal segmentable activity concentration of approximately 2 kBq/mL, we propose an administered [¹⁸F]PSMA-1007 activity of at least 1.9 and 0.4 MBq/kg for preoperative and intraoperative injections, respectively. <strong>Conclusion:</strong> Intraoperative ex vivo PET/CT is a promising modality for intraoperative margin assessment. Prospective trials are needed to further investigate the value of specimen PET/CT-based radioguided surgery in high-risk prostate cancer.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"78 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258405","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":"Positron Range Correction Helps Enhance the Image Quality of Cardiac 82Rb PET/CT","authors":"Martin Lyngby Lassen, Hunor Kertész, Ivo Rausch, Vladimir Panin, Maurizio Conti, Sven Zuehlsdorff, Jorge Cabello, Deepak Bharkhada, Robert DeKemp, Andreas Kjaer, Thomas Beyer, Philip Hasbak","doi":"10.2967/jnumed.124.267855","DOIUrl":"https://doi.org/10.2967/jnumed.124.267855","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.267855absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258488","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":"Molecular Imaging in Cancer Chemoresistance: What’s Brewing?","authors":"Luca Urso, Licia Uccelli, Alessandra Boschi, Orazio Schillaci, Luca Filippi","doi":"10.2967/jnumed.124.268967","DOIUrl":"https://doi.org/10.2967/jnumed.124.268967","url":null,"abstract":"<p>Cancer therapy has advanced with molecularly targeted approaches and immunotherapy, yet chemotherapy remains essential for many aggressive cancers, including breast, lung, ovarian, pancreatic, bladder, sarcoma, and lymphomas. A major challenge is chemoresistance, in which cancer cells evade chemotherapy’s cytotoxic effects. Overexpression of adenosine triphosphate–binding cassette transporters, especially P-glycoprotein, significantly contributes to this resistance. Thus, imaging biomarkers are urgently needed to detect P-glycoprotein overexpression in vivo, identify resistant cancer cell clones, and map their distribution and heterogeneity within tumors. This article reviews the applications of SPECT, PET, and optical imaging in addressing chemoresistance. It emphasizes the potential of these modalities to enhance cancer treatment by enabling early identification of resistant clones and improving therapeutic strategies. The article outlines key steps required for the integration of molecular imaging into clinical practice, aiming to overcome chemoresistance and optimize patient outcomes.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258490","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":"Exploring the Flare Phenomenon in Patients with Castration-Resistant Prostate Cancer: Enzalutamide-Induced PSMA Upregulation Observed on PSMA PET","authors":"Suzanne van der Gaag, André N. Vis, Imke H. Bartelink, Josephina C.C. Koppes, Marina Hodolic, Harry Hendrikse, Daniela E. Oprea-Lager","doi":"10.2967/jnumed.124.268340","DOIUrl":"https://doi.org/10.2967/jnumed.124.268340","url":null,"abstract":"<p>Androgen receptor–targeting agents, particularly enzalutamide, show promise in enhancing prostate cancer diagnostic and therapeutic strategies by modulating prostate-specific membrane antigen (PSMA). <strong>Methods:</strong> A retrospective clinical cohort study investigated 9 men with metastatic castration-resistant prostate cancer on enzalutamide. PSMA PET/CT scans were obtained before and after enzalutamide initiation to assess PSMA expression changes. Lesions and organs at risk were evaluated visually and semiquantitatively. The flare phenomenon was characterized by a significant increase (≥20%) in the SUV_max of existing lesions or the appearance of new PSMA-positive lesions. <strong>Results:</strong> Exposure to enzalutamide led to a significant PSMA expression increase in 56% of assessed lesions (<em>n</em> = 42), with new lesions detected in 1 patient (11%). PSMA expression in organs at risk remained largely unaffected, indicating a tumor-specific response. <strong>Conclusion:</strong> Enzalutamide induces PSMA upregulation in metastatic castration-resistant prostate cancer, potentially enhancing diagnostic and therapeutic strategies. Further exploration of the flare phenomenon’s clinical implications is warranted.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258397","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":"99mTc-MIP-1404 SPECT/CT Companion Diagnostic for 177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer","authors":"Thorsten Derlin, Liam Widjaja, Nina Natascha Harke, Christoph Czerner, Desiree Weiberg, Tobias L. Ross, Frank M. Bengel","doi":"10.2967/jnumed.124.269319","DOIUrl":"https://doi.org/10.2967/jnumed.124.269319","url":null,"abstract":"<p>Our objective was to determine the feasibility, diagnostic performance, and predictive value of ^99mTc-MIP-1404 SPECT in patients undergoing baseline staging and assessment of eligibility for prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy (RPT) for metastatic castration-resistant prostate cancer. <strong>Methods:</strong> Data of 46 patients undergoing ^99mTc-MIP-1404 planar scintigraphy and SPECT/CT for staging and assessment of eligibility for ¹⁷⁷Lu-PSMA RPT were retrospectively analyzed. Overall image quality was assessed, and images were visually analyzed for the presence and localization of pathologic uptake. Metastatic uptake was visually scored using a 3-point scale. ^99mTc-MIP-1404 findings were compared with the results of posttherapeutic ¹⁷⁷Lu-PSMA scans in patients subsequently commencing RPT (<em>n</em> = 35). The predictive and prognostic significance of uptake intensity in ^99mTc-MIP-1404 scans was evaluated. <strong>Results:</strong> The image quality of ^99mTc-MIP-1404 scans was rated as excellent in 98% of cases. Imaging results were concordant in 206 of 210 localizations, demonstrating almost perfect agreement with ¹⁷⁷Lu-PSMA scans (κ = 0.957 [95% CI, 0.916–0.999]). Uptake intensity higher than liver uptake identified responders (<em>P</em> = 0.0115) and was associated with prolonged progression-free survival (median, 146 vs. 96 d; hazard ratio for progression, 0.3838 [95% CI, 0.1721–0.8556]; <em>P</em> = 0.0192). In multivariable analysis, ^99mTc-MIP-1404 uptake higher than in liver emerged as an independent predictor of treatment response (odds ratio, 12.37 [95% CI, 1.613–203.3]; <em>P</em> = 0.0319). Nevertheless, 27% of responders demonstrated uptake no higher than that in the liver. <strong>Conclusion:</strong> ^99mTc-MIP-1404 imaging is suitable for assessment of eligibility for RPT in patients with advanced metastatic castration-resistant prostate cancer. In particular, pretherapeutic uptake intensity is predictive of response to ¹⁷⁷Lu-PSMA RPT.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"25 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258583","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":"Collagen Hybridizing Peptide–Based Radiotracers for Molecular Imaging of Collagen Turnover in Pulmonary Fibrosis","authors":"Azmi A. Ahmad, Mean Ghim, Gunjan Kukreja, Afarin Neishabouri, Zhengxing Zhang, Jie Li, Mani Salarian, Jakub Toczek, Kiran Gona, Keshvad Hedayatyanfard, Tian Morrison, Jiasheng Zhang, Yiyun Henry Huang, Chi Liu, S. Michael Yu, Mehran M. Sadeghi","doi":"10.2967/jnumed.124.268832","DOIUrl":"https://doi.org/10.2967/jnumed.124.268832","url":null,"abstract":"<p>Pulmonary fibrosis is a characteristic feature of interstitial lung disease. Current clinical diagnostic methods provide a snapshot of the lung structure without information on disease activity. Collagen hybridizing peptides offer the opportunity to detect collagen remodeling through their hybridization with denatured collagen. Here, we sought to develop a ^99mTc-labeled collagen hybridizing tracer to track denatured collagen in vivo and validate it in a murine model of pulmonary fibrosis. <strong>Methods:</strong> Imaging agents consisting of a polyhistidine or a poly–histidine–glutamic acid [(HE)₃] peptide connected to an N-terminal targeting moiety with 9 glycine–proline–hydroxyproline repeats [(GPO)₉] through a 3-glycine linker were synthesized. After radiolabeling with ^99mTc-tricarbonyl, the labeled products’ purity and stability were evaluated by high-performance liquid chromatography and γ-well counting, and their biodistributions were compared in mice. To induce pulmonary fibrosis, the lungs of 8- to 10-wk-old mice were exposed to bleomycin (or saline as control). At 3 wk after induction, SPECT/CT imaging with ^99mTc-(HE)₃-(GPO)₉ was performed 1 h after injection and was followed by tissue collection to assess ^99mTc-(HE)₃-(GPO)₉ biodistribution by γ-well counting and to evaluate lung histology. The specificity of the tracer uptake was assessed using a scrambled homolog. A group of animals underwent serial imaging 3 and 8–10 wk after induction. <strong>Results:</strong> The specific activity of the final radiolabeled product was 70.3 ± 14.8 GBq/µmol. Radiolabeled tracers were stable in blood for at least 2 h and showed rapid blood clearance. ^99mTc-(HE)₃-(GPO)₉ showed lower liver uptake in biodistribution studies and was selected for in vivo imaging studies. SPECT/CT imaging of bleomycin-treated mice 3 wk after induction showed higher specific ^99mTc-(HE)₃-(GPO)₉ lung uptake than that of control mice (<em>P</em> &lt; 0.01) and that of bleomycin-treated mice 8–10 wk after induction, when fibrosis was resolved (<em>P</em> &lt; 0.05). There was a significant correlation between lung uptake quantified by SPECT/CT and γ-well counting (Pearson <em>R</em> = 0.83, <em>P</em> &lt; 0.001) and significant correlations between tracer uptake and indices of tissue fibrosis. <strong>Conclusion:</strong> ^99mTc-(HE)₃-(GPO)₉ enables SPECT imaging of collagen turnover in pulmonary fibrosis. This approach expands the scope of existing diagnostic tools in fibrosis and can lead to better patient management by monitoring the effect of antifibrotic therapies.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258582","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}