EJNMMI ResearchPub 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, Ruimin Wang, Yingfang Ao
{"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, Ruimin 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":"14 1","pages":"88"},"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}
EJNMMI ResearchPub 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
{"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":"14 1","pages":"89"},"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}
EJNMMI ResearchPub 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
{"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":"14 1","pages":"87"},"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}
EJNMMI ResearchPub 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
{"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":"14 1","pages":"86"},"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}
EJNMMI ResearchPub 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
{"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":"3 1","pages":""},"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}
EJNMMI ResearchPub Date : 2024-09-12DOI: 10.1186/s13550-024-01146-x
Geng Hu, Bin Tian, Shaoli Han, Shiwei Wang, Marcus Hacker, Xiang Li, Xia Bai
{"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":"2017 1","pages":""},"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}
EJNMMI ResearchPub 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
{"title":"Potential application of [18F]AlF-PSMA-11 PET/CT in radioiodine refractory thyroid carcinoma","authors":"Bliede Van den Broeck, Jens M. Debacker, Wouter Bauters, David Creytens, Liesbeth Ferdinande, Wouter Huvenne, Bruno Lapauw, Vanessa Schelfhout, Nick Van Laeken, Charlotte Verroken","doi":"10.1186/s13550-024-01148-9","DOIUrl":"https://doi.org/10.1186/s13550-024-01148-9","url":null,"abstract":"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.","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"5 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181275","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}
EJNMMI ResearchPub 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
{"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":"60 1","pages":""},"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}
{"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":"124 1","pages":""},"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}
EJNMMI ResearchPub Date : 2024-09-04DOI: 10.1186/s13550-024-01141-2
Kim-Viktoria Bolik, Jan Hellmann, Simone Maschauer, Eduard Neu, Jürgen Einsiedel, Patrick Riss, Nora Vogg, Jörg König, Martin F Fromm, Harald Hübner, Peter Gmeiner, Olaf Prante
{"title":"Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated <sup>18</sup>F-fluorination of boroxines, in vitro and initial in vivo evaluation.","authors":"Kim-Viktoria Bolik, Jan Hellmann, Simone Maschauer, Eduard Neu, Jürgen Einsiedel, Patrick Riss, Nora Vogg, Jörg König, Martin F Fromm, Harald Hübner, Peter Gmeiner, Olaf Prante","doi":"10.1186/s13550-024-01141-2","DOIUrl":"10.1186/s13550-024-01141-2","url":null,"abstract":"<p><strong>Background: </strong>The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed in colorectal tumors. Subtype-selective OXR PET ligands suitable for in vivo use have not yet been reported. This work reports the development of <sup>18</sup>F-labeled OXR PET ligand candidates derived from the OXR antagonist suvorexant and the OX1R-selective antagonist JH112.</p><p><strong>Results: </strong>Computational analysis predicted that fluorine substitution (1e) and introduction of the fluorobenzothiazole scaffold (1f) would be suitable for maintaining high OX1R affinity. After multi-step synthesis of 1a-1f, in vitro OXR binding studies confirmed the molecular dynamics calculations and revealed single-digit nanomolar OX1R affinities for 1a-f, ranging from 0.69 to 2.5 nM. The benzothiazole 1f showed high OX1R affinity (K<sub>i</sub> = 0.69 nM), along with 77-fold subtype selectivity over OX2R. Cu-mediated <sup>18</sup>F-fluorination of boroxine precursors allowed for a shortened reaction time of 5 min to provide the non-selective OXR ligand [<sup>18</sup>F]1c and its selective OX1R congener [<sup>18</sup>F]1f in activity yields of 14% and 22%, respectively, within a total synthesis time of 52-76 min. [<sup>18</sup>F]1c and [<sup>18</sup>F]1f were stable in plasma and serum in vitro, with logD<sub>7.4</sub> of 2.28 ([<sup>18</sup>F]1c) and 2.37 ([<sup>18</sup>F]1f), and high plasma protein binding of 66% and 77%, respectively. Dynamic PET imaging in rats showed similar brain uptake of [<sup>18</sup>F]1c (0.17%ID/g) and [<sup>18</sup>F]1f (0.15%ID/g). However, preinjection of suvorexant did not significantly block [<sup>18</sup>F]1c or [<sup>18</sup>F]1f uptake in the rat brain. Pretreatment with cyclosporine A to study the role of P-glycoprotein (P-gp) in limiting brain accumulation moderately increased brain uptake of [<sup>18</sup>F]1c and [<sup>18</sup>F]1f. Accordingly, in vitro experiments demonstrated that the P-gp inhibitor zosuquidar only moderately inhibited polarized, basal to apical transport of 1c (p < 0.05) and had no effect on the transport of 1f, indicating that P-gp does not play a relevant role in brain accumulation of [<sup>18</sup>F]1c and [<sup>18</sup>F]1f in vivo.</p><p><strong>Conclusions: </strong>The in vitro and in vivo results of [<sup>18</sup>F]1c and [<sup>18</sup>F]1f provide a solid basis for further development of suitable OXR PET ligands for brain imaging.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"80"},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132176","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}