Pub Date : 2024-10-03DOI: 10.1186/s13550-024-01155-w
Marie Øbro Fosbøl, Niklas Rye Jørgensen, Peter Meidahl Petersen, Andreas Kjaer, Jann Mortensen
Background: The alpha-emitting radionuclide therapy [223Ra]RaCl2 (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.
Methods: Prospective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.
Results: A total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7-16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1-4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1-2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3-5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1-13.9), P < 0.001).
Conclusion: BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.
Trial registration: Clinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1 .
{"title":"Biomarkers of bone metabolism in [<sup>223</sup>Ra] RaCl<sub>2</sub> therapy - association with extent of disease and prediction of overall survival.","authors":"Marie Øbro Fosbøl, Niklas Rye Jørgensen, Peter Meidahl Petersen, Andreas Kjaer, Jann Mortensen","doi":"10.1186/s13550-024-01155-w","DOIUrl":"10.1186/s13550-024-01155-w","url":null,"abstract":"<p><strong>Background: </strong>The alpha-emitting radionuclide therapy [<sup>223</sup>Ra]RaCl<sub>2</sub> (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.</p><p><strong>Methods: </strong>Prospective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.</p><p><strong>Results: </strong>A total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7-16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1-4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1-2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3-5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1-13.9), P < 0.001).</p><p><strong>Conclusion: </strong>BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1186/s13550-024-01147-w
Yiqun Wang, La Li, Hongde Wang, Jin Cheng, Cancan Du, Luzheng Xu, Yifei Fan, Xiaoqing Hu, Yu Yin, Ruiming Wang, Yingfang Ao
Background: Skeletal muscles are vital for daily function, yet assessing their injuries remain challenging. We aimed to elucidate the effectiveness of 68Ga-FAPI-04 in evaluating skeletal muscle remodeling.
Results: C2C12 cells were subjected to graded H2O2 stimulation in vitro, revealing an initial rise and subsequent decline in fibroblast activation protein (FAP) expression as H2O2 concentration increased. In vivo, a murine triceps surae injury model was created using various solutions to simulate normal repair, mild repair failure, and severe repair failure. Assessments were conducted on days 1, 3, 7, and 14 using PET, MRI, and ultrasound. With 68Ga-FAPI-04, the normal and mild repair failure groups showed significantly higher SUVmax and T/B ratios on day 1 compared to the severe repair failure group. These values gradually decreased in the normal repair group, becoming negligible after day 7. MRI results for the normal repair group showed low to moderate signal intensity by day 7. A clinical study retrospectively evaluated post-hip arthroplasty patient images at intervals of 1 month, 2-3 months, 5-6 months, and over 7 months. In these patients, 18F-FDG SUVmax and volume remained relatively stable over time, while 68Ga-FAPI-04 SUVmax initially increased, then decreased, with a consistent reduction in volume.
Conclusion: In skeletal muscle injuries, FAP demonstrates a distinctive mechanism of action, and 68Ga-FAPI-04, in comparison to other tests, more precisely captures alterations in lesion site uptake intensity and volume.
Trial registration: Trial registration: ChiCTR2000041204. Registered 22 December 2020, https://www.chictr.org.cn/showproj.html?proj=66211.
{"title":"Diagnostic and evaluative efficiency of <sup>68</sup>Ga-FAPI-04 in skeletal muscle injury.","authors":"Yiqun Wang, La Li, Hongde Wang, Jin Cheng, Cancan Du, Luzheng Xu, Yifei Fan, Xiaoqing Hu, Yu Yin, Ruiming Wang, Yingfang Ao","doi":"10.1186/s13550-024-01147-w","DOIUrl":"10.1186/s13550-024-01147-w","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscles are vital for daily function, yet assessing their injuries remain challenging. We aimed to elucidate the effectiveness of <sup>68</sup>Ga-FAPI-04 in evaluating skeletal muscle remodeling.</p><p><strong>Results: </strong>C2C12 cells were subjected to graded H<sub>2</sub>O<sub>2</sub> stimulation in vitro, revealing an initial rise and subsequent decline in fibroblast activation protein (FAP) expression as H<sub>2</sub>O<sub>2</sub> concentration increased. In vivo, a murine triceps surae injury model was created using various solutions to simulate normal repair, mild repair failure, and severe repair failure. Assessments were conducted on days 1, 3, 7, and 14 using PET, MRI, and ultrasound. With <sup>68</sup>Ga-FAPI-04, the normal and mild repair failure groups showed significantly higher SUVmax and T/B ratios on day 1 compared to the severe repair failure group. These values gradually decreased in the normal repair group, becoming negligible after day 7. MRI results for the normal repair group showed low to moderate signal intensity by day 7. A clinical study retrospectively evaluated post-hip arthroplasty patient images at intervals of 1 month, 2-3 months, 5-6 months, and over 7 months. In these patients, <sup>18</sup>F-FDG SUVmax and volume remained relatively stable over time, while <sup>68</sup>Ga-FAPI-04 SUVmax initially increased, then decreased, with a consistent reduction in volume.</p><p><strong>Conclusion: </strong>In skeletal muscle injuries, FAP demonstrates a distinctive mechanism of action, and <sup>68</sup>Ga-FAPI-04, in comparison to other tests, more precisely captures alterations in lesion site uptake intensity and volume.</p><p><strong>Trial registration: </strong>Trial registration: ChiCTR2000041204. Registered 22 December 2020, https://www.chictr.org.cn/showproj.html?proj=66211.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1186/s13550-024-01154-x
Alexander Cuculiza Henriksen, Gerda Krog Thomsen, Gitte M Knudsen, Trine Stavngaard, Sverre Rosenbaum, Lisbeth Marner
Background: Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).
Case presentation: A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion.
Conclusions: The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.
背景:严重的大血管疾病可能导致脑血流动力学衰竭,严重损害脑血流(CBF)调节,增加缺血事件的风险。对病情的评估通常基于血管扩张时 CBF 的变化;然而,药物诱导的血管扩张并不能反映血流动力学衰竭导致缺血事件时的生理状况。我们将血管扩张时的[15O]H2O PET 脑扫描与正在发生的短暂性脑缺血发作(TIA)时的[99m锝]HMPAO SPECT 脑扫描进行了比较:一名肢体震颤型 TIA 患者接受了 CT、数字减影血管造影术和两种不同模式的脑灌注扫描:[15O]H2O PET 和 [99mTc]HMPAO SPECT。在 PET 扫描中使用乙酰唑胺诱导血管扩张,在 SPECT 扫描中使用生理压力(快速站立)诱导肢体震颤 TIA。CT 血管造影和数字减影血管造影显示,大脑前动脉右侧 A2 段远端闭塞,分水岭区域出现相应的梗死。大脑前动脉的主要血管区域有袢供应。在静息状态下,两种灌注模式均未显示缺血核心外的灌注减少。然而,我们发现在 TIA 期间使用乙酰唑胺进行的 PET 扫描与 SPECT 扫描之间存在明显差异。PET 扫描显示,由袢供应的血管区域相对灌注不足,而缺血核心周围区域不受影响。与此相反,SPECT 在侧支供应区域仅有轻微的相对灌注不足,而梗死核心近端分水岭区域则有明显的相对灌注不足:结论:与药理诱导的血管扩张相比,在生理刺激过程中观察到的受损区域差异对使用非生理应激物评估脑血管血流动力学提出了质疑。生理刺激试验可能会获得更具临床相关性的评估结果。
{"title":"Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics: a case report.","authors":"Alexander Cuculiza Henriksen, Gerda Krog Thomsen, Gitte M Knudsen, Trine Stavngaard, Sverre Rosenbaum, Lisbeth Marner","doi":"10.1186/s13550-024-01154-x","DOIUrl":"10.1186/s13550-024-01154-x","url":null,"abstract":"<p><strong>Background: </strong>Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [<sup>15</sup>O]H<sub>2</sub>O PET brain scan during vasodilation to a [<sup>99m</sup>Tc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA).</p><p><strong>Case presentation: </strong>A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [<sup>15</sup>O]H<sub>2</sub>O PET and [<sup>99m</sup>Tc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion.</p><p><strong>Conclusions: </strong>The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1186/s13550-024-01139-w
Shaoyu Liu, Ziqi Zhang, Jiawei Zhong, Huizhen Zhong, Yimin Fu, Lifang Liu, Xiaoting Ye, Xinlu Wang
Background: Fibroblast activation protein (FAP) has gained attention as a promising molecular target with potential utility for cancer diagnosis and therapy. [68Ga]Ga-labeled FAP-targeting peptides have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To meet the applicable demand for peptide-based FAP tracers with high patient throughput, we herein report the radiosynthesis, preclinical evaluation, and the first-in-human imaging of a novel [18F]F-labeled FAP-targeting peptide.
Results: [18F]AlF-FAP-NUR was automatedly prepared within 45 min with a non-decay corrected radiochemical yield of 18.73 ± 4.25% (n = 3). Compared to [68Ga]Ga-FAP-2286, the [18F]F-labeled peptide demonstrated more rapid, higher levels of cellular uptake and internalization, and lower levels of cellular efflux in HT1080-FAP cells. Micro-PET imaging and biodistribution studies conducted on xenograft mice models revealed a similar distribution pattern between the two tracers. However, [18F]AlF-FAP-NUR demonstrated significantly higher tumor-specific uptake resulting in improved Tumor-Background Ratios (TBRs). In the patients, a significant accumulation of [18F]AlF-FAP-NUR was found in the primary tumor. High uptake of the tracer within the bladder indicated that its major route of excretion was through urine.
Conclusions: Based on the physical imaging properties and longer half-life of [18F]F, [18F]AlF-FAP-NUR exhibited promising characteristics such as enhanced tumor-specific accumulation and elevated TBRs, which made it a viable candidate for further clinical investigation.
{"title":"Preclinical evaluation and first-in-human study of [<sup>18</sup>F]AlF-FAP-NUR for PET imaging cancer-associated fibroblasts.","authors":"Shaoyu Liu, Ziqi Zhang, Jiawei Zhong, Huizhen Zhong, Yimin Fu, Lifang Liu, Xiaoting Ye, Xinlu Wang","doi":"10.1186/s13550-024-01139-w","DOIUrl":"10.1186/s13550-024-01139-w","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast activation protein (FAP) has gained attention as a promising molecular target with potential utility for cancer diagnosis and therapy. [<sup>68</sup>Ga]Ga-labeled FAP-targeting peptides have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To meet the applicable demand for peptide-based FAP tracers with high patient throughput, we herein report the radiosynthesis, preclinical evaluation, and the first-in-human imaging of a novel [<sup>18</sup>F]F-labeled FAP-targeting peptide.</p><p><strong>Results: </strong>[<sup>18</sup>F]AlF-FAP-NUR was automatedly prepared within 45 min with a non-decay corrected radiochemical yield of 18.73 ± 4.25% (n = 3). Compared to [<sup>68</sup>Ga]Ga-FAP-2286, the [<sup>18</sup>F]F-labeled peptide demonstrated more rapid, higher levels of cellular uptake and internalization, and lower levels of cellular efflux in HT1080-FAP cells. Micro-PET imaging and biodistribution studies conducted on xenograft mice models revealed a similar distribution pattern between the two tracers. However, [<sup>18</sup>F]AlF-FAP-NUR demonstrated significantly higher tumor-specific uptake resulting in improved Tumor-Background Ratios (TBRs). In the patients, a significant accumulation of [<sup>18</sup>F]AlF-FAP-NUR was found in the primary tumor. High uptake of the tracer within the bladder indicated that its major route of excretion was through urine.</p><p><strong>Conclusions: </strong>Based on the physical imaging properties and longer half-life of [<sup>18</sup>F]F, [<sup>18</sup>F]AlF-FAP-NUR exhibited promising characteristics such as enhanced tumor-specific accumulation and elevated TBRs, which made it a viable candidate for further clinical investigation.</p><p><strong>Trial registration: </strong>www.Chictr.org.cn , ChiCTR2300076976 Retrospectively registered 25 October 2023. at, URL: https://www.chictr.org.cn/showproj.html?proj=206753 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27DOI: 10.1186/s13550-024-01151-0
Katarína Benčurová, Loan Tran, Joachim Friske, Kajetana Bevc, Thomas H Helbich, Marcus Hacker, Michael Bergmann, Markus Zeitlinger, Alexander Haug, Markus Mitterhauser, Gerda Egger, Theresa Balber
Background: Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient - in vitro PDOs - in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns.
Results: The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking.
Conclusions: We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients.
{"title":"An in vivo tumour organoid model based on the chick embryonic chorioallantoic membrane mimics key characteristics of the patient tissue: a proof-of-concept study.","authors":"Katarína Benčurová, Loan Tran, Joachim Friske, Kajetana Bevc, Thomas H Helbich, Marcus Hacker, Michael Bergmann, Markus Zeitlinger, Alexander Haug, Markus Mitterhauser, Gerda Egger, Theresa Balber","doi":"10.1186/s13550-024-01151-0","DOIUrl":"https://doi.org/10.1186/s13550-024-01151-0","url":null,"abstract":"<p><strong>Background: </strong>Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient - in vitro PDOs - in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns.</p><p><strong>Results: </strong>The main liver metastasis of the CRC patient exhibited high 2-[<sup>18</sup>F]FDG uptake and moderate and focal [<sup>68</sup>Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[<sup>18</sup>F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient's liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient's sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [<sup>68</sup>Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [<sup>68</sup>Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking.</p><p><strong>Conclusions: </strong>We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient's tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [<sup>68</sup>Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[<sup>18</sup>F]FDG was avidly taken up in the patient's liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1186/s13550-024-01150-1
Jonathan Sigfridsson, Tomasz Baron, Johannes Bergsten, Hendrik J. Harms, Jonny Nordström, Tanja Kero, Patrik Svanström, Elin Lindström, Lieuwe Appel, My Jonasson, Mark Lubberink, Frank A. Flachskampf, Jens Sörensen
Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate. LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.
心脏正电子发射断层扫描(PET)可通过一次动态扫描对灌注和左心室(LV)功能进行无创评估。然而,目前还没有通过 PET 评估二尖瓣反流严重程度的先例。对 PET 数据应用指标稀释技术和门控图像分析可以计算前向搏量和左心室总搏量。与心血管磁共振(CMR)相比,我们的目的是评估结合这些方法使用动态 15O 水和 11C 醋酸 PET 测量反流容积(RegVol)和反流分数(RegF)的效果。21 名患有严重原发性二尖瓣反流的患者接受了当天的动态 PET(15O-水和 11C-乙酸酯)和 CMR 检查。正电子发射计算机断层显像数据被重建为动态序列,其中包括第一次扫描的短时间帧、门控 15O 水血池图像和门控 11C 醋酸心肌摄取图像。基于 PET 的 RegVol 和 RegF 与 CMR 密切相关(RegVol:15O-水 r = 0.94,11C-醋酸 r = 0.91;RegF:15O-水 r = 0.88,11C-醋酸 r = 0.84,p 30mL),15O-水为 95%,11C-醋酸为 92%。使用心脏 PET 定量的左心室反流严重程度与 CMR 相关,在区分患者和健康志愿者方面显示出很高的准确性。
{"title":"Quantitation of mitral regurgitation using positron emission tomography","authors":"Jonathan Sigfridsson, Tomasz Baron, Johannes Bergsten, Hendrik J. Harms, Jonny Nordström, Tanja Kero, Patrik Svanström, Elin Lindström, Lieuwe Appel, My Jonasson, Mark Lubberink, Frank A. Flachskampf, Jens Sörensen","doi":"10.1186/s13550-024-01150-1","DOIUrl":"https://doi.org/10.1186/s13550-024-01150-1","url":null,"abstract":"Cardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR). Twenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate. LV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s13550-024-01148-9
Bliede Van den Broeck, Jens M. Debacker, Wouter Bauters, David Creytens, Liesbeth Ferdinande, Wouter Huvenne, Bruno Lapauw, Vanessa Schelfhout, Nick Van Laeken, Charlotte Verroken
Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [18F]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging. Recent case series have shown promising results regarding the role of the prostate-specific membrane antigen (PSMA) in TC. In this study we explored the value of [18F]AlF-PSMA-11 PET/CT in RAI-R TC. In this phase II study, lesions detected on [18F]AlF-PSMA-11 PET were compared to findings from [18F]FDG PET/CT. Additionally, the serologic soluble prostate-specific membrane antigen (sPSMA) was measured using ELISA. PSMA-expression on tumor tissue in any available resection specimens was analysed with an immunostainer. Eight patients were included, with a total of 39 identified lesions based on PET imaging. [18F]AlF-PSMA-11 PET identified 30 of 39 lesions, and [18F]FDG PET identified 33 lesions, leading to a detection rate of 76.9% and 84.6%, respectively. Interestingly, while nine lesions were solely visualized on [18F]FDG, six were uniquely seen on [18F]AlF-PSMA-11 PET. While sPSMA was immeasurable in all female patients, no correlation was found between sPSMA in male patients and disease-related factors. In five out of eight patients immunohistology showed PSMA expression on the primary tumor. Although not all lesions could be visualized, [18F]PSMA-11 PET identified multiple lesions imperceptible on [18F]FDG PET. These results display the potential additional diagnostic role of PSMA-targeted imaging in patients with RAI-R TC. Trial registration number No. EudraCT 2021-000456-19.
被诊断为放射性碘难治性(RAI-R)甲状腺癌(TC)患者的预后明显差于放射性敏感性甲状腺癌患者。这些难治性恶性肿瘤通常已发生分化,阻碍了碘成像的有效性。此外,使用[18F]FDG PET/CT 进行代谢成像在这些病例中的作用也很有限,因此对 RAI-R TC 进行充分分期具有挑战性。最近的病例系列显示,前列腺特异性膜抗原(PSMA)在前列腺癌中的作用很有希望。在这项研究中,我们探讨了[18F]AlF-PSMA-11 PET/CT 在 RAI-R TC 中的价值。在这项 II 期研究中,[18F]AlF-PSMA-11 PET 检测到的病变与[18F]FDG PET/CT 的结果进行了比较。此外,还使用酶联免疫吸附法测定了血清可溶性前列腺特异性膜抗原(sPSMA)。使用免疫印迹仪分析切除标本中肿瘤组织的 PSMA 表达。共纳入了八名患者,根据 PET 成像共确定了 39 个病灶。在 39 个病灶中,[18F]AlF-PSMA-11 PET 发现了 30 个,[18F]FDG PET 发现了 33 个,检出率分别为 76.9% 和 84.6%。有趣的是,[18F]FDG PET 只能发现 9 个病灶,而[18F]AlF-PSMA-11 PET 则能发现 6 个病灶。虽然所有女性患者的 sPSMA 都无法测量,但男性患者的 sPSMA 与疾病相关因素之间并无关联。八名患者中有五名患者的免疫组织学检查显示原发肿瘤上有 PSMA 表达。虽然并非所有病灶都能被观察到,但[18F]PSMA-11 PET 发现了[18F]FDG PET 无法察觉的多个病灶。这些结果显示了 PSMA 靶向成像在 RAI-R TC 患者中的潜在诊断作用。试验注册号:EudraCT 2021-000456-19。
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Pub Date : 2024-09-12DOI: 10.1186/s13550-024-01146-x
Geng Hu, Bin Tian, Shaoli Han, Shiwei Wang, Marcus Hacker, Xiang Li, Xia Bai
<p>Glioma, a primary malignant tumor originating from glial cells, represents approximately 81% of intracranial malignant tumors. It is known for its high heterogeneity and generally poor prognosis [1,2,3]. Despite comprehensive treatment approaches, the prognosis for glioma remains grim due to its highly malignant nature [4]. Surgical intervention, primarily through routine craniotomy, has been the traditional treatment method, although it involves significant trauma and has long lacked an ideal approach. Conventional surgical treatments showed a high recurrence rate, necessitating supplementary postoperative radiotherapy and chemotherapy [5, 6].</p><p>Recent studies emphasize the critical role of postoperative radiotherapy, particularly intensity-modulated radiotherapy [7]. This technique offers precise targeting and dose concentration, effectively eliminating glioma while minimizing radiation exposure to surrounding healthy tissues [7]. Traditional imaging may lead to misinterpretations of therapeutic outcomes, such as pseudo-progression, where treatment may initially seem to worsen tumor imaging or symptoms, yet these can improve if the current treatment plan is maintained [8, 9].</p><p>Innovations in PET imaging with <sup>11</sup>C or <sup>18</sup>F-labeled choline (CHO) have shown promise in tumor diagnostics. CHO enters cells via high-affinity choline transporters, is phosphorylated by choline kinase, and integrated into phosphatidylcholine, reflecting the synthesis activity of the cell membrane system [10, 11]. CHO uptake is low in normal brain tissue but significantly higher in rapidly proliferating tumor cells. Several quantitative markers, such as maximum standardized uptake value (SUV<sub>max</sub>), average standardized uptake value (SUV<sub>mean</sub>), metabolic tumor volume (MTV), total lesion CHO uptake (TLG), and the tumor-to-normal contralateral cortical activity ratio (T/N ratio), have proven crucial for correlating with glioma grading. These markers offer prognostic distinctions superior to those based on the World Health Organization (WHO) grading system [12, 13].</p><p>Utilizing <sup>11</sup>C-CHO PET/CT imaging technology, type, location, and extent of tumors could be pinpointed more accurately. This method not only facilitates precise pre-surgical diagnoses and tumor boundary delineation but also provides insights into the tumor’s biological characteristics and invasiveness. Such detailed information is vital for crafting personalized treatment plans and for surgical planning, thereby optimizing surgical outcomes and minimizing risks. Postoperatively, <sup>11</sup>C-CHO PET/CT imaging is invaluable for monitoring treatment response, evaluating residual tumors, assessing recurrence risks, and improving overall prognosis [14, 15].</p><p>This pilot study retrospectively analyzed 38 patients with recurrent glioma, as determined by <sup>11</sup>C-CHO PET/CT imaging. The findings affirm the significant prognostic value of this
创作共用 "许可协议允许以任何媒介或格式进行非商业性使用、共享、分发和复制,但必须注明原作者和来源,提供 "创作共用 "许可协议的链接,并说明是否修改了许可材料。根据本许可协议,您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出了许可使用范围,则您需要直接获得版权所有者的许可。如需查看该许可的副本,请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleHu, G., Tian, B., Han, S. et al. Prognostic evaluation in recurrent glioma through 11C-Choline PET/CT imaging.EJNMMI Res 14, 84 (2024). https://doi.org/10.1186/s13550-024-01146-xDownload citationReceived:03 June 2024Accepted: 29 August 2024Published: 12 September 2024DOI: https://doi.org/10.1186/s13550-024-01146-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Prognostic evaluation in recurrent glioma through 11C-Choline PET/CT imaging","authors":"Geng Hu, Bin Tian, Shaoli Han, Shiwei Wang, Marcus Hacker, Xiang Li, Xia Bai","doi":"10.1186/s13550-024-01146-x","DOIUrl":"https://doi.org/10.1186/s13550-024-01146-x","url":null,"abstract":"<p>Glioma, a primary malignant tumor originating from glial cells, represents approximately 81% of intracranial malignant tumors. It is known for its high heterogeneity and generally poor prognosis [1,2,3]. Despite comprehensive treatment approaches, the prognosis for glioma remains grim due to its highly malignant nature [4]. Surgical intervention, primarily through routine craniotomy, has been the traditional treatment method, although it involves significant trauma and has long lacked an ideal approach. Conventional surgical treatments showed a high recurrence rate, necessitating supplementary postoperative radiotherapy and chemotherapy [5, 6].</p><p>Recent studies emphasize the critical role of postoperative radiotherapy, particularly intensity-modulated radiotherapy [7]. This technique offers precise targeting and dose concentration, effectively eliminating glioma while minimizing radiation exposure to surrounding healthy tissues [7]. Traditional imaging may lead to misinterpretations of therapeutic outcomes, such as pseudo-progression, where treatment may initially seem to worsen tumor imaging or symptoms, yet these can improve if the current treatment plan is maintained [8, 9].</p><p>Innovations in PET imaging with <sup>11</sup>C or <sup>18</sup>F-labeled choline (CHO) have shown promise in tumor diagnostics. CHO enters cells via high-affinity choline transporters, is phosphorylated by choline kinase, and integrated into phosphatidylcholine, reflecting the synthesis activity of the cell membrane system [10, 11]. CHO uptake is low in normal brain tissue but significantly higher in rapidly proliferating tumor cells. Several quantitative markers, such as maximum standardized uptake value (SUV<sub>max</sub>), average standardized uptake value (SUV<sub>mean</sub>), metabolic tumor volume (MTV), total lesion CHO uptake (TLG), and the tumor-to-normal contralateral cortical activity ratio (T/N ratio), have proven crucial for correlating with glioma grading. These markers offer prognostic distinctions superior to those based on the World Health Organization (WHO) grading system [12, 13].</p><p>Utilizing <sup>11</sup>C-CHO PET/CT imaging technology, type, location, and extent of tumors could be pinpointed more accurately. This method not only facilitates precise pre-surgical diagnoses and tumor boundary delineation but also provides insights into the tumor’s biological characteristics and invasiveness. Such detailed information is vital for crafting personalized treatment plans and for surgical planning, thereby optimizing surgical outcomes and minimizing risks. Postoperatively, <sup>11</sup>C-CHO PET/CT imaging is invaluable for monitoring treatment response, evaluating residual tumors, assessing recurrence risks, and improving overall prognosis [14, 15].</p><p>This pilot study retrospectively analyzed 38 patients with recurrent glioma, as determined by <sup>11</sup>C-CHO PET/CT imaging. The findings affirm the significant prognostic value of this ","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s13550-024-01149-8
Kian Baradaran-Salimi, Amir Karimzadeh, Berthold Voges, Ivayla Apostolova, Thomas Sauvigny, Olga Simova, Michael Lanz, Susanne Klutmann, Stefan Stodieck, Philipp T. Meyer, Ralph Buchert
Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. 177 patients (48% females, median age 38y, interquartile range 27–48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: “interictal only” (interictal SPECT and statistical hypoperfusion map), “ictal only” (ictal SPECT and hyperperfusion map), and “full” setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence” if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the “full” setting was used as reference standard. The proportion of “lateralizing with high confidence” cases was 4.5/31.6/38.4% in the “interictal only”/“ictal only”/“full” setting. One (12.5%) of the 8 cases that were “lateralizing with high confidence” in the “interictal only” setting lateralized to the wrong hemisphere. Among the 56 cases that were “lateralizing with high confidence” in the “ictal only” setting, 54 (96.4%) were also lateralizing in the “full” setting, all to the same hemisphere. Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.
{"title":"Brain perfusion SPECT in the presurgical evaluation of epilepsy: is additional ictal SPECT required in case of high-confidence lateralization of the seizure onset zone by interictal SPECT and vice versa?","authors":"Kian Baradaran-Salimi, Amir Karimzadeh, Berthold Voges, Ivayla Apostolova, Thomas Sauvigny, Olga Simova, Michael Lanz, Susanne Klutmann, Stefan Stodieck, Philipp T. Meyer, Ralph Buchert","doi":"10.1186/s13550-024-01149-8","DOIUrl":"https://doi.org/10.1186/s13550-024-01149-8","url":null,"abstract":"Ictal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT. 177 patients (48% females, median age 38y, interquartile range 27–48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: “interictal only” (interictal SPECT and statistical hypoperfusion map), “ictal only” (ictal SPECT and hyperperfusion map), and “full” setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered \"lateralizing with high confidence” if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the “full” setting was used as reference standard. The proportion of “lateralizing with high confidence” cases was 4.5/31.6/38.4% in the “interictal only”/“ictal only”/“full” setting. One (12.5%) of the 8 cases that were “lateralizing with high confidence” in the “interictal only” setting lateralized to the wrong hemisphere. Among the 56 cases that were “lateralizing with high confidence” in the “ictal only” setting, 54 (96.4%) were also lateralizing in the “full” setting, all to the same hemisphere. Starting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142223783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques. In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.
氟-18脱氧葡萄糖([18F]FDG)正电子发射断层扫描/计算机断层扫描(PET/CT)在诊断肝内胆管癌(ICC)方面存在一些局限性。我们对同时接受[18F]FDG和18F标记成纤维细胞活化蛋白抑制剂([18F]FAPI)-04 PET/CT检查的组织学确诊ICC患者进行了前瞻性分析。通过配对 Wilcoxon 符号秩检验和 Mann-Whitney U 检验比较了两种方法的最大标准摄取值(SUVmax)、肿瘤与背景比(TBR)、代谢肿瘤体积(MTV)、总病灶糖酵解(TLG)、[18F]FAPI-avid 肿瘤体积(FTV)、总病灶成纤维细胞活化蛋白表达(TLF),并用 McNemar 检验评估了两种技术的诊断准确性。共纳入了 23 名患者的 389 个病灶。与[18F]FDG相比,[18F]F-FAPI-04 PET/CT对肝内病变(86.3% 对 78.2%,P = 0.040)、淋巴结转移(85.2% 对 68.2%,P = 0.007)、腹膜转移(100% 对 93.8%)和骨转移(100% 对 70.5%,P < 0.001)的检出率更高。在非胆管炎肝内病变中,[18F]FAPI-04 PET显示出比[18F]FDG PET更高的SUVmax、TBR和更大的肿瘤负荷值(SUVmax:8.7 vs. 6.4,P <0.001;TBR:8.0 vs. 3.5,P <0.001;FTV vs. MTV:41.3 vs. 12.4,P <0.001):41.3 vs. 12.4,P < 0.001;TLF vs. TLG:223.5 vs. 57.0,P < 0.001)、淋巴结转移(SUVmax:6.5 vs. 5.5,P = 0.042;TBR:5.4 vs. 3.9,P < 0.001;FTV vs. MTV:2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024)和骨转移(SUVmax:9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001)。然而,在6例阻塞性胆管炎患者中,[18F]FDG的放射性示踪剂摄取量(SUVmax:14.7 vs. 8.4,P < 0.001;TBR:7.4 vs. 2.8,P < 0.001)高于[18F]FAPI-04 PET/CT。与[18F]FDG相比,[18F]FAPI-04 PET/CT 使 23 例患者中的 6 例(26.1%)改变了治疗计划。与[18F]FDG PET/CT 相比,[18F]FAPI-04 PET/CT 对肝内病灶、淋巴结转移和远处转移(尤其是骨转移)的检出率和放射性示踪剂摄取率更高。因此,[18F]FAPI-04 PET/CT 可能是一种很有前途的 ICC 诊断和分期技术。临床试验,NCT05485792。2022年8月1日注册,回顾性注册,https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1。
{"title":"Role of [18F]FAPI-04 in staging and therapeutic management of intrahepatic cholangiocarcinoma: prospective comparison with [18F]FDG PET/CT","authors":"Jiucen Liang, Shuqin Jiang, Jingjing Song, Danyang Chen, Shaojuan Weng, Shuyi Li, Hao Peng, Zhidong Liu, Jing Zhang, Yuanlin Chen, Songquan Rao, Haipeng Chen, Rusen Zhang, Hao Liu, Linqi Zhang","doi":"10.1186/s13550-024-01145-y","DOIUrl":"https://doi.org/10.1186/s13550-024-01145-y","url":null,"abstract":"Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI–avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann–Whitney U test, and McNemar’s test was used to assess the diagnostic accuracy between the two techniques. In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}