EJNMMI Research最新文献

{"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}

{"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":"&lt;p&gt;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].&lt;/p&gt;&lt;p&gt;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].&lt;/p&gt;&lt;p&gt;Innovations in PET imaging with &lt;sup&gt;11&lt;/sup&gt;C or &lt;sup&gt;18&lt;/sup&gt;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&lt;sub&gt;max&lt;/sub&gt;), average standardized uptake value (SUV&lt;sub&gt;mean&lt;/sub&gt;), 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].&lt;/p&gt;&lt;p&gt;Utilizing &lt;sup&gt;11&lt;/sup&gt;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, &lt;sup&gt;11&lt;/sup&gt;C-CHO PET/CT imaging is invaluable for monitoring treatment response, evaluating residual tumors, assessing recurrence risks, and improving overall prognosis [14, 15].&lt;/p&gt;&lt;p&gt;This pilot study retrospectively analyzed 38 patients with recurrent glioma, as determined by &lt;sup&gt;11&lt;/sup&gt;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}

{"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}

{"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}

{"title":"Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated ¹⁸F-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 ¹⁸F-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_i = 0.69 nM), along with 77-fold subtype selectivity over OX2R. Cu-mediated ¹⁸F-fluorination of boroxine precursors allowed for a shortened reaction time of 5 min to provide the non-selective OXR ligand [¹⁸F]1c and its selective OX1R congener [¹⁸F]1f in activity yields of 14% and 22%, respectively, within a total synthesis time of 52-76 min. [¹⁸F]1c and [¹⁸F]1f were stable in plasma and serum in vitro, with logD_7.4 of 2.28 ([¹⁸F]1c) and 2.37 ([¹⁸F]1f), and high plasma protein binding of 66% and 77%, respectively. Dynamic PET imaging in rats showed similar brain uptake of [¹⁸F]1c (0.17%ID/g) and [¹⁸F]1f (0.15%ID/g). However, preinjection of suvorexant did not significantly block [¹⁸F]1c or [¹⁸F]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 [¹⁸F]1c and [¹⁸F]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 [¹⁸F]1c and [¹⁸F]1f in vivo.</p><p><strong>Conclusions: </strong>The in vitro and in vivo results of [¹⁸F]1c and [¹⁸F]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}

{"title":"Neuromelanin-targeted 18 F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques.","authors":"Hongyan Feng, Ning Tu, Ke Wang, Xiaowei Ma, Zhentao Zhang, Zhongchun Liu, Zhen Cheng, Lihong Bu","doi":"10.1186/s13550-024-01136-z","DOIUrl":"10.1186/s13550-024-01136-z","url":null,"abstract":"<p><strong>Background: </strong>Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-¹⁸F-5-fluoropicolinamide (¹⁸F-P3BZA), which was initially developed for the imaging of melanoma. ¹⁸F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether ¹⁸F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.</p><p><strong>Results: </strong>¹⁸F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. ¹⁸F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. ¹⁸F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of ¹⁸F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, ¹⁸F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, ¹⁸F-P3BZA uptake in B16F10 tumors could be blocked by excess cold ¹⁹F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI ¹⁸F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In in vitro autoradiography studies ¹⁸F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.</p><p><strong>Conclusion: </strong>¹⁸F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"79"},"PeriodicalIF":3.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119269","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}

{"title":"Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [¹⁸F]FECNT-d₄.","authors":"Jie Tang, Congjin Liu, Chunyi Liu, Qianyue Hu, Yi Fang, Zhengping Chen","doi":"10.1186/s13550-024-01140-3","DOIUrl":"10.1186/s13550-024-01140-3","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[¹⁸F]-fluoroethyl) nortropane ([¹⁸F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [¹⁸F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[¹⁸F]-fluoroethyl-1,1,2,2-d4) nortropane ([¹⁸F]FECNT-d₄), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [¹⁸F]FECNT-d₄ to detect dopaminergic neuron degeneration in Parkinson's disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections.</p><p><strong>Results: </strong>PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [¹⁸F]FECNT-d₄ uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure.</p><p><strong>Conclusion: </strong>Our findings demonstrate that [¹⁸F]FECNT-d₄ accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson's disease.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"78"},"PeriodicalIF":3.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105496","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}

{"title":"Validation of the C-X-C chemokine receptor 3 (CXCR3) as a target for PET imaging of T cell activation.","authors":"Sebastian Martin, Lennard Wendlinger, Béatrice Zitti, Mehdi Hicham, Viktoriia Postupalenko, Léo Marx, Greta Giordano-Attianese, Elisabetta Cribioli, Melita Irving, Alexandra Litvinenko, Radmila Faizova, David Viertl, Margret Schottelius","doi":"10.1186/s13550-024-01142-1","DOIUrl":"10.1186/s13550-024-01142-1","url":null,"abstract":"<p><strong>Purpose: </strong>CXCR3 is expressed on activated T cells and plays a crucial role in T-cell recruitment to the tumor microenvironment (TME) during cell-based and immune checkpoint inhibitor (ICI) immunotherapy. This study utilized a ⁶⁴Cu-labeled NOTA-α-CXCR3 antibody to assess CXCR3 expression in the TME and validate it as a potential T cell activation biomarker in vivo.</p><p><strong>Procedures: </strong>CXCR3⁺ cells infiltrating MC38 tumors (B57BL/6 mice, untreated and treated with αPD-1/αCTLA-4 ICI) were quantified using fluorescence microscopy and flow cytometry. A commercial anti-mouse CXCR3 antibody (α-CXCR3) was site-specifically conjugated with 2,2,2-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) and radiolabeled with ⁶⁴Cu. Saturation binding of [⁶⁴Cu]Cu-NOTA-α-CXCR3 was investigated using CHO cells stably transfected with murine CXCR3. Biodistribution and PET imaging studies both at baseline and after 1 to 3 cycles of ICI, respectively, were carried out using different molar activities (10 GBq/µmol to 300 GBq/µmol) of [⁶⁴Cu]Cu-NOTA-α-CXCR3.</p><p><strong>Results: </strong>Flow cytometry analysis at baseline confirmed the presence of CXCR3 + T-cells in MC38 tumors, which was significantly increased at day five after ICI (treated 33.8 ± 17.4 vs. control 8.8 ± 6.2 CD3⁺CXCR3⁺ cells/mg). These results were qualitatively and quantitatively confirmed by immunofluorescence of tumor cryoslices. In vivo PET imaging of MC38 tumor bearing mice before, during and after ICI using [⁶⁴Cu]Cu-NOTA-α-CXCR3 (Kd = 3.3 nM) revealed a strong dependence of CXCR3-specificity of tracer accumulation in secondary lymphoid organs on molar activity. At 300 GBq/µmol (1.5 µg of antibody/mouse), a specific signal was observed in lymph nodes (6.33 ± 1.25 control vs. 3.95 ± 1.23%IA/g blocking) and the spleen (6.04 ± 1.02 control vs. 3.84 ± 0.79%IA/g blocking) at 48 h p.i. Spleen-to-liver ratios indicated a time dependent systemic immune response showing a steady increase from 1.08 ± 0.19 (untreated control) to 1.54 ± 0.14 (three ICI cycles).</p><p><strong>Conclusions: </strong>This study demonstrates the feasibility of in vivo imaging of CXCR3 upregulation under immunotherapy using antibodies. However, high molar activities and low antibody doses are essential for sensitive detection in lymph nodes and spleen. Detecting therapy-induced changes in CXCR3⁺ T cell numbers in tumors was challenging due to secondary antibody-related effects. Nonetheless, CXCR3 remains a promising target for imaging T cell activation, with anticipated improvements in sensitivity using alternative tracers with high affinities and favorable pharmacokinetics.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"77"},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079714","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}

{"title":"A radioligand for in vitro autoradiography of CSF1R in post-mortem CNS tissues.","authors":"Catherine A Foss, Ravi Naik, Deepankar Das, Hyojin Cha, Il Minn, Andrew Hall, Paige Finley, Sophia Jiang Wu, Yong Du, Robert F Dannals, Martin G Pomper, Andrew G Horti","doi":"10.1186/s13550-024-01133-2","DOIUrl":"10.1186/s13550-024-01133-2","url":null,"abstract":"<p><strong>Background: </strong>Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer's dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [³H]1 and [¹¹C]1. The PET imaging properties of [¹¹C]1 in mice and baboon were investigated. [³H]1 was studied in B_max measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [¹¹C]iodomethane or [³H]iodomethane to produce [¹¹C]1 and [³H]1, respectively. Ex vivo brain biodistribution of [¹¹C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [³H]1 was performed in frozen sections using a standard saturation binding technique.</p><p><strong>Results: </strong>Compound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [¹¹C]1 was synthesized with high yield. [³H]1 was synthesized similarly (commercially). Biodistribution of [¹¹C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [¹¹C]1 was ~ 50% specific for CSF1R. PET/CT [¹¹C]1 study in baboon revealed low brain uptake (0.36 SUV) of [¹¹C]1. Autoradiography with [³H]1 gave significantly elevated B_max values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter.</p><p><strong>Conclusions: </strong>Compound 1 exhibits a high in vitro CSF1R binding affinity. [¹¹C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood-brain barrier in baboon PET. [³H]1 specifically labels CSF1R in post-mortem human brain. The binding of [³H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"76"},"PeriodicalIF":3.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055244","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}