{"title":"A study method using early dynamic acquisition of [<sup>18</sup>F]fluorodopa positron emission tomography for the differential diagnosis between progression and radionecrosis of brain metastases after radiotherapy.","authors":"Ines Barrat, Marc-Etienne Meyer, Alexandre Coutte, Mathieu Boone, Roger Bouzerar, Pascal Bailly","doi":"10.1186/s13550-024-01158-7","DOIUrl":"10.1186/s13550-024-01158-7","url":null,"abstract":"<p><strong>Background: </strong>It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of <sup>18</sup>F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (<sup>18</sup>F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing <sup>18</sup>F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion's voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean).</p><p><strong>Results: </strong>Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%.</p><p><strong>Conclusion: </strong>The <sup>18</sup>F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388961","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 : 2024-10-08DOI: 10.1186/s13550-024-01153-y
Suvi Hartikainen, Ville Vepsäläinen, Tiina Laitinen, Marja Hedman, Tomi Laitinen, Tuomo Tompuri
{"title":"Heparin does not improve myocardial glucose metabolism suppression in [18 F]FDG PET/CT in patients with low β-hydroxybutyrate level.","authors":"Suvi Hartikainen, Ville Vepsäläinen, Tiina Laitinen, Marja Hedman, Tomi Laitinen, Tuomo Tompuri","doi":"10.1186/s13550-024-01153-y","DOIUrl":"10.1186/s13550-024-01153-y","url":null,"abstract":"<p><strong>Background: </strong>Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [<sup>18</sup>F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [<sup>18</sup>F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [<sup>18</sup>F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [<sup>18</sup>F]FDG-PET/CT.</p><p><strong>Results: </strong>155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15-20 min before [<sup>18</sup>F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [<sup>18</sup>F]FDG uptake pattern was evaluated visually and [<sup>18</sup>F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1-5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875).</p><p><strong>Conclusions: </strong>While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388962","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 : 2024-10-08DOI: 10.1186/s13550-024-01138-x
Philipp Backhaus, Keith S Pentlow, Alan L Ho, Audrey Mauguen, James A Fagin, Naga Vara Kishore Pillarsetty, Serge K Lyashchenko, Eva Burnazi, Ronald A Ghossein, Shalini Chhabra, Murad Abusamra, Steven M Larson, Heiko Schöder, Joseph O'Donoghue, Wolfgang Weber, Ravinder K Grewal
{"title":"[<sup>18</sup>F]TFB PET/CT misses intense [<sup>124</sup>I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer.","authors":"Philipp Backhaus, Keith S Pentlow, Alan L Ho, Audrey Mauguen, James A Fagin, Naga Vara Kishore Pillarsetty, Serge K Lyashchenko, Eva Burnazi, Ronald A Ghossein, Shalini Chhabra, Murad Abusamra, Steven M Larson, Heiko Schöder, Joseph O'Donoghue, Wolfgang Weber, Ravinder K Grewal","doi":"10.1186/s13550-024-01138-x","DOIUrl":"10.1186/s13550-024-01138-x","url":null,"abstract":"<p><strong>Background: </strong>Fluorine 18-labelled tetrafluoroborate ([<sup>18</sup>F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [<sup>18</sup>F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [<sup>18</sup>F]TFB and compare its properties to [<sup>124</sup>I]IodinePET/CT in patients with metastatic thyroid cancer.</p><p><strong>Methods: </strong>Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [<sup>18</sup>F]TFB and were given 230 ± 9 MBq [<sup>124</sup>I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [<sup>124</sup>I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [<sup>18</sup>F]TFB and [<sup>124</sup>I]Iodine were calculated.</p><p><strong>Results: </strong>Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [<sup>18</sup>F]TFB and 30 (91%) on [<sup>124</sup>I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [<sup>124</sup>I]Iodine PET/CT with a median SUV<sub>max</sub> of 3.3 (range, 0.4-285.0). All of these lesions were [<sup>18</sup>F]TFB-negative.</p><p><strong>Conclusion: </strong>[<sup>18</sup>F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer.</p><p><strong>Trial registration number: </strong>NCT03196518, registered on June 22, 2017.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388960","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 : 2024-10-03DOI: 10.1186/s13550-024-01155-w
Marie Øbro Fosbøl, Niklas Rye Jørgensen, Peter Meidahl Petersen, Andreas Kjaer, Jann Mortensen
{"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450107/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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":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}
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":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}
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":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}
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":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}
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":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}
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":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":"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}