The Journal of Nuclear Medicine最新文献

{"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}

{"title":"177Lu-Labeled Anticlaudin 6 Monoclonal Antibody for Targeted Therapy in Esophageal Cancer","authors":"Huan Du, Xiaofei Hao, Binwei Lin, Mingming Tang, Decai Wang, Xia Yang, Jing Wang, Liling Qin, Yuchuan Yang, Xiaobo Du","doi":"10.2967/jnumed.124.268487","DOIUrl":"https://doi.org/10.2967/jnumed.124.268487","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.268487absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258489","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, Dosimetry, and Feasibility of [68Ga]Ga-PSMA-R2 as an Imaging Agent in Patients with Biochemical Recurrence or Metastatic Prostate Cancer","authors":"Liza Lindenberg, Thomas A. Hope, Frank I. Lin, Steven P. Rowe, Darko Pucar, Noella Gilbert, Daniela Chicco, Beilei He, Benedikt Feuerecker, Elena Castaldi, Lilja B. Solnes","doi":"10.2967/jnumed.124.268318","DOIUrl":"https://doi.org/10.2967/jnumed.124.268318","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.268318absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258491","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":"Preclinical Evaluation of 68Ga/177Lu-Labeled FAP-Targeted Peptide for Tumor Radiopharmaceutical Imaging and Therapy","authors":"Rang Wang, Mingxing Huang, Weichen Wang, Mufeng Li, Yingwei Wang, Rong Tian","doi":"10.2967/jnumed.124.268689","DOIUrl":"https://doi.org/10.2967/jnumed.124.268689","url":null,"abstract":"<p>Fibroblast activation protein (FAP) has been considered a promising target for tumor imaging and therapy. This study designed a novel peptide, FAP-HXN, specifically targeting FAP and exhibiting significant potential as a radionuclide-labeled theranostic agent. Preclinical studies were conducted to evaluate the potency, selectivity, and efficacy of FAP-HXN. <strong>Methods:</strong> FAP-HXN was synthesized and characterized for selectivity and specificity toward FAP. Cellular uptake of the radiolabeled FAP-HXN in human embryonic kidney (HEK)-293-FAP cells with high expressions of FAP was evaluated. The diagnostic and therapeutic potential of ⁶⁸Ga- and ¹⁷⁷Lu-labeled radioligands was evaluated in HEK-293-FAP tumor-bearing mice compared with the FAP-targeting peptide FAP-2286. <strong>Results:</strong> FAP-HXN demonstrated high binding ability to human and mouse sources of FAP. Moreover, the in vivo studies confirmed the high affinity and specificity of radiolabeled FAP-HXN. Small-animal PET imaging demonstrated that [⁶⁸Ga]Ga-FAP-HXN had continuous tumor uptake in FAP-positive tumors after administration compared with [⁶⁸Ga]Ga-FAP-2286. In the therapeutic experiments, [¹⁷⁷Lu]Lu-FAP-HXN showed significant antitumor activity in HEK-293-FAP xenografts at well-tolerated doses, which also exhibited longer tumor retention and better tumor growth inhibition compared with [¹⁷⁷Lu]Lu-FAP-2286. <strong>Conclusion:</strong> The preclinical studies revealed that radiolabeled FAP-HXN had high tumor uptake, prolonged retention, and significant anticancer efficacy in HEK-293-FAP xenografts. FAP-HXN shows promising potential as a novel theranostic radioligand for FAP-positive tumors.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026337","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":"Diuresis During 18F-Flotufolastat (rhPSMA-7.3) PET/CT Improves Recurrence Detection After Prostatectomy: A Prospective Phase II Trial","authors":"Ismaheel O. Lawal, Aliza Mushtaq, Ashesh B. Jani, Manali Rupji, Vishal R. Dhere, Sagar A. Patel, Mehmet A. Bilen, Pretesh R. Patel, Nikhil T. Sebastian, Jeffrey M. Switchenko, David M. Schuster, Charles Marcus","doi":"10.2967/jnumed.124.268574","DOIUrl":"https://doi.org/10.2967/jnumed.124.268574","url":null,"abstract":"<p>Radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have emerged as a sensitive tool for PET imaging of prostate cancer (PCa) recurrence. Yet urinary bladder activity may obscure the visualization of prostate bed recurrence. Among the Food and Drug Administration–approved PSMA radiopharmaceuticals, ¹⁸F-flotufolastat (rhPSMA-7.3) has the lowest urinary excreted activity. We investigated the impact of diuresis with intravenous furosemide and oral hydration on bladder activity and PCa recurrence detection in patients with PCa after prostatectomy with biochemical recurrence. <strong>Methods:</strong> This phase II study (NCT05779943) prospectively recruited men with PCa after prostatectomy with a rising prostate-specific antigen (PSA) level of at least 0.1 ng/mL. All patients had 2 ¹⁸F-flotufolastat PET/CT scans, one with 20 mg of furosemide administered intravenously with the radiotracer and the other without. SUV_mean, SUV_max, and bladder volume were compared between the with- and without-furosemide PET/CT studies. PCa lesion detection was compared between the 2 sets of scans. <strong>Results:</strong> Twenty men with a median PSA of 0.61 ng/mL (interquartile range, 0.18–1.15) completed both sets of scans. Bladder activity was significantly lower for the with- than the without-furosemide studies, at a median SUV_max of 4.20 (range, 1.70–19.80) versus 13.35 (range, 3.90–165.4), respectively (<em>P</em> = 0.014), and a median SUV_mean of 2.95 (range, 0.80–17.60) versus 10.00 (range, 1.90–140.00), respectively (<em>P</em> = 0.017). Multivariable analysis demonstrated that both furosemide administration and bladder distention were independent covariates for reduced bladder activity. At the prostate bed region level, the recurrence detection rates were 17 of 20 (85%) and 12 of 20 (60%) for the with- and without-furosemide studies, respectively (<em>P</em> = 0.025). No difference in detection rates was present at the per-patient, pelvic, or extrapelvic regions between the 2 sets of studies. Three of 20 without-furosemide studies had a mild noninterfering peribladder halo artifact, but none had an artifact with furosemide. <strong>Conclusion:</strong> In men with biochemical recurrence and a PSA level of at least 0.1 ng/mL after prostatectomy for PCa, a strategy with ¹⁸F-flotufolastat PET/CT and concordant low-dose furosemide further reduces urinary bladder intensity and increases local recurrence detection. Even without the use of a diuretic, relative bladder distension alone also reduces bladder activity, though not to the same degree as with a diuretic.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026708","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":"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}