EJNMMI Research最新文献

{"title":"Significant reduction of activity retention in the kidneys via optimized linker sequences in radiohybrid-based minigastrin analogs.","authors":"Nadine Holzleitner, Sebastian Fischer, Isabel Maniyankerikalam, Roswitha Beck, Constantin Lapa, Hans-Jürgen Wester, Thomas Günther","doi":"10.1186/s13550-024-01087-5","DOIUrl":"10.1186/s13550-024-01087-5","url":null,"abstract":"<p><strong>Background: </strong>We recently introduced radiohybrid (rh)-based minigastrin analogs e.g., DOTA-rhCCK-18 (DOTA-D-Dap(p-SiFA)-(D-γ-Glu)₈-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH₂), that revealed substantially increased activity retention in the tumor. However, one major drawback of these first generation rh-based cholecystokinin-2 receptor (CCK-2R) ligands is their elevated activity levels in the kidneys, especially at later time points (24 h p.i.). Therefore, this study aimed to reduce kidney retention with regard to a therapeutic use via substitution of negatively charged D-glutamic acid moieties by hydrophilic uncharged polyethylene glycol (PEG) linkers of various length ((PEG)₄ to (PEG)₁₁). Furthermore, the influence of differently charged silicon-based fluoride acceptor (SiFA)-moieties (p-SiFA: neutral, SiFA-ipa: negatively charged, and SiFAlin: positively charged) on in vitro properties of minigastrin analogs was evaluated. Out of all compounds evaluated in vitro, the two most promising minigastrin analogs were further investigated in vivo.</p><p><strong>Results: </strong>CCK-2R affinity of most compounds evaluated was found to be in a range of 8-20 nM (by means of apparent IC₅₀), while ligands containing a SiFA-ipa moiety displayed elevated IC₅₀ values. Lipophilicity was noticeably lower for compounds containing a D-γ-glutamate (D-γ-Glu) moiety next to the D-Dap(SiFA) unit as compared to their counterparts lacking the additional negative charge. Within this study, combining the most favorable CCK-2R affinity and lipophilicity, [^177/natLu]Lu-DOTA-rhCCK-70 (DOTA-D-Dap(p-SiFA)-D-γ-Glu-(PEG)₇-D-γ-Glu-(PEG)₃-Trp-(N-Me)Nle-Asp-1-Nal-NH₂; IC₅₀: 12.6 ± 2.0 nM; logD_7.4: - 1.67 ± 0.08) and [^177/natLu]Lu-DOTA-rhCCK-91 (DOTA-D-Dap(SiFAlin)-D-γ-Glu-(PEG)₄-D-γ-Glu-(PEG)₃-Trp-(N-Me)Nle-Asp-1-Nal-NH₂; IC₅₀: 8.6 ± 0.7 nM; logD_7.4 =  - 1.66 ± 0.07) were further evaluated in vivo. Biodistribution data of both compounds revealed significantly reduced (p < 0.0001) activity accumulation in the kidneys compared to [¹⁷⁷Lu]Lu-DOTA-rhCCK-18 at 24 h p.i., leading to enhanced tumor-to-kidney ratios despite lower tumor uptake. However, overall tumor-to-background ratios of the novel compounds were lower than those of [¹⁷⁷Lu]Lu-DOTA-rhCCK-18.</p><p><strong>Conclusion: </strong>We could show that the reduction of negative charges within the linker section of radiohybrid-based minigastrin analogs led to decreased activity levels in the kidneys at 24 h p.i., while maintaining a good tumor uptake. Thus, favorable tumor-to-kidney ratios were accomplished in vivo. However, further optimization has to be done in order to improve tumor retention and general biodistribution profile.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012450","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":"Pharmacodynamics and biodistribution of [195mPt]cisplatin(CISSPECT®) in head and neck squamous cell carcinoma.","authors":"Reinout H de Roest, Marijke Stigter van Walsum, Karlijn van der Schilden, Ruud H Brakenhoff","doi":"10.1186/s13550-024-01082-w","DOIUrl":"10.1186/s13550-024-01082-w","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin- based chemoradiotherapy is a crucial pillar in the treatment of HNSCC. The use of cisplatin comes with high toxicity rates as 35% of patients cannot sustain the planned dose while response is unpredictable. Unfortunately, there are no clinically applicable biomarkers to predict response. Based on the association of response with the number of DNA adducts and the involved molecular pathway to resolve cisplatin-induced DNA crosslinks in HNSCC, [195mPt]cisplatin (CISSPECT®) might have potential to monitor drug uptake and retention before treatment, and predict cisplatin response. The aim of this study is to investigate this concept by analyzing uptake, retention and biodistribution of [195mPt]cisplatin between known cisplatin-sensitive (VU-SCC-1131) and -resistant (VU-SCC-OE) HNSCC cell lines in vitro and xenografted in mice in vivo.</p><p><strong>Results: </strong>By a variety of experiments in vitro, including cell cycle analyses, and in vivo, the sensitivity of cell line VU-SCC-1131 and resistance of cell line VU-SCC-OE for cisplatin was demonstrated. VU-SCC-OE was able to accumulate more [195mPt]cisplatin in the DNA, and showed an increased capability to repair [195mPt]cisplatin crosslinks compared to VU-SCC-1131. Notably, DNA binding of cisplatin increased even when cisplatin was removed from the medium, likely from intracellular sources. In vivo, [195mPt]cisplatin showed a rapid biodistribution to the large organs such as the liver, with no differences between intravenous and intraperitoneal administration. Most circulating [195mPt]cisplatin was cleared by renal filtration, and accumulation in kidney and liver remained high. Uptake in xenografts was rapid (blood:tumor ratio; 1:1) and highest after 1 h, while decreasing after 6 h in line with the concentration in the blood. Remarkably, there was no significant difference in uptake or retention between xenografts of the cisplatin-sensitive and -resistant cell line.</p><p><strong>Conclusion: </strong>VU-SCC-1131 with a known FA deficiency and VU-SCC-OE displayed a significant difference in sensitivity to and recovery from cisplatin treatment, due to S-phase problems in VU-SCC-1131 at low doses, in line with the genetic defect. Using Pt-195m radioactivity analysis, we demonstrated the limited capability of cisplatin crosslink repair in VU-SCC-1131. Unexpectedly, we were not able to translate these findings to a mouse model for sensitivity prediction based on the biodistribution in the tumor, most likely as other factors such as influx counterbalanced repair. These data do not support response prediction by [195mPt]cisplatin, and applications to predict the toxic side-effects of cisplatin and to tailor dosing schemes seem more feasible.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995921","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":"The efficacy of short acquisition time using ¹⁸F-FDG total-body PET/CT for the identification of pediatric epileptic foci.","authors":"Min Li, Xiao Cui, Huixin Yue, Chao Ma, Kun Li, Leiying Chai, Min Ge, Hui Li, Yee Ling Ng, Yun Zhou, Jianguo Shi, Yanhua Duan, Zhaoping Cheng","doi":"10.1186/s13550-024-01081-x","DOIUrl":"10.1186/s13550-024-01081-x","url":null,"abstract":"<p><strong>Background: </strong>¹⁸F-FDG positron emission tomography (PET) plays a crucial part in the evaluation for pediatric epileptic patients prior to therapy. Short-term scanning holds significant importance, especially for pediatrics epileptic individuals who exhibited involuntary movements. The aim was to evaluate the effects of short acquisition time on image quality and lesion detectability in pediatric epileptic patients using total-body (TB) PET/CT. A total of 25 pediatric patients who underwent TB PET/CT using uEXPLORER scanner with an ¹⁸F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Short acquisition times (60 s, 150 and 300 s) were simulated by truncating PET data in list mode to reduce count density. Subjective image quality was scored on a 5-point scale. Regions of interest analysis of suspected epileptogenic zones (EZs), corresponding locations contralateral to EZs, and healthy cerebellar cortex were used to compare the semi-quantitative uptake indices of short-time images and then were compared with 600 s images. The comparison of EZs detectability based on time-dependent PET images was performed.</p><p><strong>Results: </strong>Our study demonstrated that a short acquisition time of 150 s is sufficient to maintain subjective image quality and lesion significance. Statistical analysis revealed no significant difference in subjective PET image quality between imaging at 300 s and 150 s (P > 0.05). The overall impression scores of image quality and lesion conspicuity in G60s were both greater than 3 (overall quality, 3.21 ± 0.46; lesion conspicuity, 4.08 ± 0.74). As acquisition time decreased, the changes of SUVmax and SD in the cerebellar cortex gradually increased (P < 0.01). There was no significant difference in asymmetry index (AI) difference between the groups and the AIs of EZs were > 15% in all groups. In 26 EZs of 25 patients, the lesion detection rate was still 100% when the time was reduced to 60 s.</p><p><strong>Conclusions: </strong>This study proposed that TB PET/CT acquisition time could be reduced to 60 s with acceptable lesion detectability. Furthermore, it was suggested that a 150 s acquisition time would be sufficient to achieve diagnostic performance and image quality for children with epilepsy.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971435","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 therapeutic effect and prognostic value of ¹⁸F-FDG PET/CT in different treatment nodes of DLBCL patients.","authors":"Wenyu Zhao, Xiaodong Wu, Shuo Huang, Hui Wang, Hongliang Fu","doi":"10.1186/s13550-024-01074-w","DOIUrl":"10.1186/s13550-024-01074-w","url":null,"abstract":"<p><strong>Background: </strong>In the present study, we aimed to investigate the role of baseline (B), interim (I) and end-of-treatment (Eot) ¹⁸F-FDG PET/CT in assessing the prognosis of diffuse large B cell lymphoma (DLBCL), so as to identify patients who need intensive treatment at an early stage.</p><p><strong>Methods: </strong>A total of 127 DLBCL patients (62 men; 65 women; median age 62 years) were retrospectively analyzed in this study. Baseline (n = 127), interim (n = 127, after 3-4 cycles) and end-of-treatment (n = 53, after 6-8 cycles) PET/CT images were re-evaluated; semi-quantitative parameters such as maximum standardized uptake value of lesion-to-liver ratio (SUVmax_(LLR)) and lesion-to-mediastinum ratio (SUVmax_(LMR)), total metabolic tumor volume (TMTV) and total metabolic tumor volume (TLG) were recorded. ΔTLG¹ was the change of interim relative to baseline TLG (I to B), ΔTLG² (Eot to B). ΔSUVmax and ΔTMTV were the same algorithm. The visual Deauville 5-point scale (D-5PS) has been adopted as the major criterion for PET evaluation. Visual analysis (VA) and semi-quantitative parameters were assessed for the ability to predict progression-free survival (PFS) and overall survival (OS) by using Kaplan-Meier method, cox regression and logistic regression analysis. When visual and semi-quantitative analysis are combined, the result is only positive if both are positive.</p><p><strong>Results: </strong>At a median follow-up of 34 months, the median PFS and OS were 20 and 32 months. The survival curve analysis showed that advanced stage and IPI score with poor prognosis, ΔSUVmax_(LLR)¹ < 89.2%, ΔTMTV¹ < 91.8% and ΔTLG¹ < 98.8%, ΔSUVmax_(LLR)² < 86.4% were significantly related to the shortening of PFS in patient (p < 0.05). ΔSUVmax_(LLR)¹ < 83.2% and ΔTLG¹ < 97.6% were significantly correlated with the shortening of OS in patients (p < 0.05). Visual analysis showed that incomplete metabolic remission at I-PET and Eot-PET increased the risk of progress and death. In terms of predicting recurrence by I-PET, the combination of visual and semi-quantitative parameters showed higher positive predictive value (PPV) and specificity than a single index.</p><p><strong>Conclusion: </strong>Three to four cycles of R-CHOP treatment may be a time point for early prediction of early recurrence/refractory (R/R) patients and active preemptive treatment. Combined visual analysis with semi-quantitative parameters of ¹⁸F-FDG PET/CT at interim can improve prognostic accuracy and may allow for more precise screening of patients requiring early intensive therapy.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899537","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":"Synthesis and preclinical evaluation of [¹¹C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor.","authors":"Antonia A Högnäsbacka, Alex J Poot, Christophe Plisson, Jonas Bergare, David R Bonsall, Stuart P McCluskey, Lisa A Wells, Esther Kooijman, Robert C Schuit, Mariska Verlaan, Wissam Beaino, Guus A M S van Dongen, Danielle J Vugts, Charles S Elmore, Jan Passchier, Albert D Windhorst","doi":"10.1186/s13550-024-01078-6","DOIUrl":"10.1186/s13550-024-01078-6","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the epidermal growth factor receptor (EGFR) kinase domain are common in non-small cell lung cancer. Conventional tyrosine kinase inhibitors target the mutation site in the ATP binding pocket, thereby inhibiting the receptor's function. However, subsequent treatment resistance mutations in the ATP binding site are common. The EGFR allosteric inhibitor, EAI045, is proposed to have an alternative mechanism of action, disrupting receptor signaling independent of the ATP-binding site. The antibody cetuximab is hypothesized to increase the number of accessible allosteric pockets for EAI045, thus increasing the potency of the inhibitor. This work aimed to gain further knowledge on pharmacokinetics, the EGFR mutation-targeting potential, and the influence of cetuximab on the uptake by radiolabeling EAI045 with carbon-11 and tritium.</p><p><strong>Results: </strong>2-(5-fluoro-2-hydroxyphenyl)-2-((2-iodobenzyl)amino)-N-(thiazol-2-yl)acetamide and 2-(5-fluoro-2-hydroxyphenyl)-N-(5-iodothiazol-2-yl)-2-(1-oxoisoindolin-2-yl)acetamide were synthesized as precursors for the carbon-11 and tritium labeling of EAI045, respectively. [¹¹C]EAI045 was synthesized using [¹¹C]CO in a palladium-catalyzed ring closure in a 10 ± 1% radiochemical yield (decay corrected to end of [¹¹C]CO₂ production), > 97% radiochemical purity and 26 ± 1 GBq/µmol molar activity (determined at end of synthesis) in 51 min. [³H]EAI045 was synthesized by a tritium-halogen exchange in a 0.2% radiochemical yield, 98% radiochemical purity, and 763 kBq/nmol molar activity. The ability of [¹¹C]EAI045 to differentiate between L858R/T790M mutated EGFR expressing H1975 xenografts and wild-type EGFR expressing A549 xenografts was evaluated in female nu/nu mice. The uptake was statistically significantly higher in H1975 xenografts compared to A549 xenografts (0.45 ± 0.07%ID/g vs. 0.31 ± 0.10%ID/g, P = 0.0166). The synergy in inhibition between EAI045 and cetuximab was evaluated in vivo and in vitro. While there was some indication that cetuximab influenced the uptake of [³H]EAI045 in vitro, this could not be confirmed in vivo when tumor-bearing mice were administered cetuximab (0.5 mg), 24 h prior to injection of [¹¹C]EAI045.</p><p><strong>Conclusions: </strong>EAI045 was successfully labeled with tritium and carbon-11, and the in vivo results indicated [¹¹C]EAI045 may be able to distinguish between mutated and non-mutated EGFR in non-small cell lung cancer mouse models. Cetuximab was hypothesized to increase EAI045 uptake; however, no significant effect was observed on the uptake of [¹¹C]EAI045 in vivo or [³H]EAI045 in vitro in H1975 xenografts and cells.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740724","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":"Non-specific irreversible ⁸⁹Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using ⁸⁹Zr-immuno-PET.","authors":"Jessica E Wijngaarden, Yvonne W S Jauw, Gerben J C Zwezerijnen, Berlinda J de Wit-van der Veen, Daniëlle J Vugts, Josée M Zijlstra, Guus A M S van Dongen, Ronald Boellaard, C Willemien Menke-van der Houven van Oordt, Marc C Huisman","doi":"10.1186/s13550-024-01079-5","DOIUrl":"10.1186/s13550-024-01079-5","url":null,"abstract":"<p><strong>Background: </strong>Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the ⁸⁹Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on ⁸⁹Zr-immuno-PET data of biopsy-proven target-negative tumours. Data of two studies, including target status obtained from biopsies, were retrospectively analysed, and Patlak linearization provided the net rate of irreversible uptake (K_i).</p><p><strong>Results: </strong>Two tumours were classified as CD20-negative and two as CD20-positive. Four tumours were classified as CEA-negative and nine as CEA-positive. K_i values of CD20-negative (0.43 µL/g/h and 0.92 µL/g/h) and CEA-negative tumours (mdn = 1.97 µL/g/h, interquartile range (IQR) = 1.50-2.39) were higher than zero. Median K_i values of target-negative tumours were lower than CD20-positive (1.87 µL/g/h and 1.90 µL/g/h) and CEA-positive tumours (mdn = 2.77 µL/g/h, IQR = 2.11-3.65).</p><p><strong>Conclusion: </strong>Biopsy-proven target-negative tumours showed irreversible uptake of ⁸⁹Zr-mAbs measured in vivo using ⁸⁹Zr-immuno-PET data, which suggests the presence of non-specific irreversible uptake in tumours. Consequently, for ⁸⁹Zr-immuno-PET, even if the target is absent, a tumour-to-plasma ratio always increases over time.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734728","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":"Relaxed fibronectin: a potential novel target for imaging endometriotic lesions.","authors":"Belinda Trachsel, Stefan Imobersteg, Giulia Valpreda, Gad Singer, Regula Grabherr, Mark Ormos, Irene A Burger, Rahel A Kubik-Huch, Roger Schibli, Viola Vogel, Martin Béhé","doi":"10.1186/s13550-024-01070-0","DOIUrl":"10.1186/s13550-024-01070-0","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis is characterized by the ectopic occurrence of endometrial tissue. Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI are often unable to detect all lesions, and a clear correlation between imaging and clinical symptoms is still controversial. Therefore, it was our aim to identify a potential target to image active endometriotic lesions.</p><p><strong>Results: </strong>For our studies, we employed the preclinical radiotracer [¹¹¹In]In-FnBPA5, which specifically binds to relaxed fibronectin-an extracellular matrix protein with key functions in homeostasis that has been implicated in the pathogenesis of diseases such as cancer and fibrosis. We employed this tracer in biodistribution as well as SPECT/CT studies in mice and conducted immunohistochemical stainings on mouse uterine tissue as well as on patient-derived endometriosis tissue. In biodistribution and SPECT/CT studies using the radiotracer [¹¹¹In]In-FnBPA5, we found that radiotracer uptake in the myometrium varies with the estrous cycle of the mouse, leading to higher uptake of [¹¹¹In]In-FnBPA5 during estrogen-dependent phases, which indicates an increased abundance of relaxed fibronectin when estrogen levels are high. Finally, immunohistochemical analysis of patient samples demonstrated that there is preferential relaxation of fibronectin in the proximity of the endometriotic stroma.</p><p><strong>Conclusion: </strong>Estrous cycle stages characterized by high estrogen levels result in a higher abundance of relaxed fibronectin in the murine myometrium. This finding together with a first proof-of-concept study employing human endometriosis tissues suggests that relaxed fibronectin could be a potential target for the development of a diagnostic radiotracer targeting endometriotic lesions. With [¹¹¹In]In-FnBPA5, the matching targeting molecule is in preclinical development.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715960","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":"Exploring the impact of PEGylation on pharmacokinetics: a size-dependent effect of polyethylene glycol on prostate-specific membrane antigen inhibitors.","authors":"Yang Liu, Li Xia, Haiyang Li, Ping Cai, Sufan Tang, Yue Feng, Guangfu Liu, Yue Chen, Nan Liu, Wei Zhang, Zhijun Zhou","doi":"10.1186/s13550-024-01071-z","DOIUrl":"10.1186/s13550-024-01071-z","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer-related deaths in men. Prostate-specific membrane antigen (PSMA) as a target has gained increasing attention. This research aims to investigate and understand how altering size of PEG impacts the in vitro and in vivo behavior and performance of PSMA inhibitors, with a specific focus on their pharmacokinetic characteristics and targeting properties.</p><p><strong>Results: </strong>Two ⁶⁸Ga-labeled PSMA-targeted radiotracers were developed, namely [⁶⁸Ga]Ga-PP4-WD and [⁶⁸Ga]Ga-PP8-WD, with varying sizes of polyethylene glycol (PEG). [⁶⁸Ga]Ga-PP4-WD and [⁶⁸Ga]Ga-PP8-WD had excellent affinity for PSMA with IC50 being 8.06 ± 0.91, 6.13 ± 0.79 nM, respectively. Both tracers enabled clear visualization of LNCaP tumors in PET images with excellent tumor-to-background contrast. They also revealed highly efficient uptake and internalization into LNCaP cells, increasing over time. The biodistribution studies demonstrated that both radioligands exhibited significant and specific uptake into LNCaP tumors. Furthermore, they were rapidly cleared through the renal pathway, as evidenced by [⁶⁸Ga]Ga-PP4-WD and [⁶⁸Ga]Ga-PP8-WD showing a tenfold and a fivefold less in renal uptake, respectively, compared to [⁶⁸Ga]Ga-Flu-1 in 30 min. Both in vitro and in vivo experiments demonstrated that PEG size significantly impacted tumor-targeting and pharmacokinetic properties.</p><p><strong>Conclusions: </strong>These radiotracers have demonstrated their effectiveness in significantly reducing kidney uptake while maintaining the absorbed dose in tumors. Both radiotracers exhibited strong binding and internalization characteristics in vitro, displayed high specificity and affinity for PSMA in vivo.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697155","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":"Spherization indices measured by resting SPECT improve risk stratification in patients with ischemia with non-obstructive coronary artery disease (INOCA).","authors":"Yuting Zhao, Yingqi Hu, Yuanyuan Li, Yanhui Wang, Yuxin Xiao, Li Xu, Tailin Ren, Qiuyan Wu, Ruonan Wang, Zhifang Wu, Sijin Li, Ping Wu","doi":"10.1186/s13550-024-01075-9","DOIUrl":"10.1186/s13550-024-01075-9","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of ischemia with non-obstructive coronary artery disease (INOCA) is substantial, but its risk stratification has been suboptimal. Resting SPECT myocardial perfusion imaging (MPI) could provide useful heart information including spherical indices. We aimed to evaluate the prognostic value of spherical indices in individuals with INOCA.</p><p><strong>Results: </strong>During a median follow-up of 47.2 ± 20.8 months, 49 (17.2%) patients experienced major adverse cardiac events (MACE). Compared to those without MACE, those with MACE had a higher shape index (SI) (0.60 ± 0.07 vs. 0.58 ± 0.06; P = 0.028) and a lower E2 (eccentricity index calculated by the QPS) (0.81 ± 0.05 vs. 0.83 ± 0.04; P = 0.019). MACE event-free survival analysis revealed significant differences in the SI and E2 among all patients (all log-rank P < 0.01). Multivariate Cox analysis showed abnormal SI (HR: 2.73, 95% CI 1.44-5.18, P = 0.002) and E2 (HR: 1.94, 95% CI 1.08-3.48, P = 0.026) were both independent predictors for MACE when they were put into the same model, respectively. The incorporation of the SI into the baseline model demonstrated a significant improvement in the predictive accuracy for MACEs (P = 0.026), whereas E2 did not exhibit a similar improvement (P > 0.05).</p><p><strong>Conclusion: </strong>For patients with INOCA, spherical indices (especially the SI) were associated with long-term MACE, which could be a preferable indicator for risk stratification and prognostic prediction.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697168","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":"The image quality and feasibility of solitary delayed [⁶⁸ Ga]Ga-PSMA-11 PET/CT using long field-of-view scanning in patients with prostate cancer.","authors":"Xiaofeng Yu, Lian Xu, Gang Huang, Jianjun Liu, Ruohua Chen, Yumei Chen","doi":"10.1186/s13550-024-01076-8","DOIUrl":"10.1186/s13550-024-01076-8","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that delayed [⁶⁸ Ga]Ga-PSMA PET/CT imaging improves lesion detection compared to early [⁶⁸ Ga]Ga-PSMA PET/CT in patients with prostate cancer. However, the sole use of delayed [⁶⁸ Ga]Ga-PSMA PET/CT has been limited due to the insufficient number of photons obtained with standard PET/CT scanners. The combination of early and delayed [⁶⁸ Ga]Ga-PSMA standard PET/CT may be considered, and it is challenging to incorporate into a high-demand clinical setting. Long field-of-view (LFOV) PET/CT scanners have higher sensitivity compared to standard PET/CT. However, it remains unknown whether the image quality of solitary delayed [⁶⁸ Ga]Ga-PSMA LFOV PET/CT imaging is adequate to satisfy clinical diagnostic requirements. Therefore, the purpose of this study was to evaluate the image quality of delayed [⁶⁸ Ga]Ga-PSMA LFOV PET/CT and examine the feasibility of utilizing delayed [⁶⁸ Ga]Ga-PSMA LFOV PET/CT imaging alone in patients with prostate cancer.</p><p><strong>Methods: </strong>The study sample consisted of 56 prostate cancer patients who underwent [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT scanning between December 2020 and July 2021. All patients were subjected to early LFOV PET/CT imaging at 1-h post-injection as well as delayed LFOV PET/CT imaging at 3-h post-injection using [⁶⁸ Ga]Ga-PSMA-11. The image quality and diagnostic efficiency of solitary delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT imaging was analyzed.</p><p><strong>Results: </strong>The results showed that delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT yielded satisfactory image quality that fulfilled clinical diagnostic benchmarks. Compared to early imaging, delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT demonstrated heightened lesion SUVmax values (11.0 [2.3-193.6] vs. 7.0 [2.0-124.3], P < 0.001) and superior tumor-to-background ratios (3.3 [0.5-62.2] vs. 1.7 [0.3-30.7], P < 0.001). Additionally, delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT detected supplementary lesions in 14 patients (25%) compared to early imaging, resulting in modifications to disease staging and management plans.</p><p><strong>Conclusions: </strong>In summary, the findings indicate that the image quality of delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT is satisfactory for meeting clinical diagnostic prerequisites. The use of solitary delayed [⁶⁸ Ga]Ga-PSMA-11 LFOV PET/CT imaging in prostate cancer simplifies the examination protocol and improves patient compliance, compared to [⁶⁸ Ga]Ga-PSMA-11 standard PET/CT which necessitates both early and delayed imaging.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691521","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}