EJNMMI ResearchPub Date : 2024-09-03DOI: 10.1186/s13550-024-01136-z
Hongyan Feng, Ning Tu, Ke Wang, Xiaowei Ma, Zhentao Zhang, Zhongchun Liu, Zhen Cheng, Lihong Bu
{"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)-<sup>18</sup>F-5-fluoropicolinamide (<sup>18</sup>F-P3BZA), which was initially developed for the imaging of melanoma. <sup>18</sup>F-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 <sup>18</sup>F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.</p><p><strong>Results: </strong><sup>18</sup>F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. <sup>18</sup>F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. <sup>18</sup>F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of <sup>18</sup>F-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, <sup>18</sup>F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, <sup>18</sup>F-P3BZA uptake in B16F10 tumors could be blocked by excess cold <sup>19</sup>F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI <sup>18</sup>F-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 <sup>18</sup>F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.</p><p><strong>Conclusion: </strong><sup>18</sup>F-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}
EJNMMI ResearchPub Date : 2024-08-29DOI: 10.1186/s13550-024-01140-3
Jie Tang, Congjin Liu, Chunyi Liu, Qianyue Hu, Yi Fang, Zhengping Chen
{"title":"Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [<sup>18</sup>F]FECNT-d<sub>4</sub>.","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-[<sup>18</sup>F]-fluoroethyl) nortropane ([<sup>18</sup>F]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 [<sup>18</sup>F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[<sup>18</sup>F]-fluoroethyl-1,1,2,2-d4) nortropane ([<sup>18</sup>F]FECNT-d<sub>4</sub>), 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 [<sup>18</sup>F]FECNT-d<sub>4</sub> 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, [<sup>18</sup>F]FECNT-d<sub>4</sub> 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 [<sup>18</sup>F]FECNT-d<sub>4</sub> 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}
EJNMMI ResearchPub Date : 2024-08-28DOI: 10.1186/s13550-024-01142-1
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
{"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 <sup>64</sup>Cu-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<sup>+</sup> 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 <sup>64</sup>Cu. Saturation binding of [<sup>64</sup>Cu]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 [<sup>64</sup>Cu]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<sup>+</sup>CXCR3<sup>+</sup> 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 [<sup>64</sup>Cu]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<sup>+</sup> 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}
EJNMMI ResearchPub Date : 2024-08-26DOI: 10.1186/s13550-024-01133-2
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
{"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 [<sup>3</sup>H]1 and [<sup>11</sup>C]1. The PET imaging properties of [<sup>11</sup>C]1 in mice and baboon were investigated. [<sup>3</sup>H]1 was studied in B<sub>max</sub> 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 [<sup>11</sup>C]iodomethane or [<sup>3</sup>H]iodomethane to produce [<sup>11</sup>C]1 and [<sup>3</sup>H]1, respectively. Ex vivo brain biodistribution of [<sup>11</sup>C]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 [<sup>3</sup>H]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). [<sup>11</sup>C]1 was synthesized with high yield. [<sup>3</sup>H]1 was synthesized similarly (commercially). Biodistribution of [<sup>11</sup>C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [<sup>11</sup>C]1 was ~ 50% specific for CSF1R. PET/CT [<sup>11</sup>C]1 study in baboon revealed low brain uptake (0.36 SUV) of [<sup>11</sup>C]1. Autoradiography with [<sup>3</sup>H]1 gave significantly elevated B<sub>max</sub> 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. [<sup>11</sup>C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood-brain barrier in baboon PET. [<sup>3</sup>H]1 specifically labels CSF1R in post-mortem human brain. The binding of [<sup>3</sup>H]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}
EJNMMI ResearchPub Date : 2024-08-25DOI: 10.1186/s13550-024-01137-y
Dong Yun Lee, Jungsu S Oh, Ji Wan Kim, Seung Hun Lee, Beom-Jun Kim, Jung-Min Koh, Jae Seung Kim, Jin-Sook Ryu
{"title":"Imaging bone turnover assessment through volumetric density-adjusted standardized uptake value using quantitative bone SPECT/CT in osteoporosis.","authors":"Dong Yun Lee, Jungsu S Oh, Ji Wan Kim, Seung Hun Lee, Beom-Jun Kim, Jung-Min Koh, Jae Seung Kim, Jin-Sook Ryu","doi":"10.1186/s13550-024-01137-y","DOIUrl":"10.1186/s13550-024-01137-y","url":null,"abstract":"<p><strong>Background: </strong>Serum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [<sup>99m</sup>Tc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUV<sub>mean</sub>, g/cm<sup>3</sup>) and volumetric bone mineral density (vBMD, mg/cm<sup>3</sup>) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUV<sub>mean</sub>) was calculated by dividing the SUV<sub>mean</sub> by the vBMD and multiplying by 1,000.</p><p><strong>Results: </strong>SUV<sub>mean</sub> correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUV<sub>mean</sub> correlated negatively with vBMD (ρ = -0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUV<sub>mean</sub>. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUV<sub>mean</sub> (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover.</p><p><strong>Conclusion: </strong>Volumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"75"},"PeriodicalIF":3.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055245","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 : 2024-08-22DOI: 10.1186/s13550-024-01134-1
Lindsay K Dickerson, Adrienne L Lehnert, Donald K Hamlin, Kevin P Labadie, Kristin E Goodsell, Yongjun Liu, Yawen Li, D Scott Wilbur, Robert Miyaoka, James O Park
{"title":"Pilot study of humanized glypican-3-targeted zirconium-89 immuno-positron emission tomography for hepatocellular carcinoma.","authors":"Lindsay K Dickerson, Adrienne L Lehnert, Donald K Hamlin, Kevin P Labadie, Kristin E Goodsell, Yongjun Liu, Yawen Li, D Scott Wilbur, Robert Miyaoka, James O Park","doi":"10.1186/s13550-024-01134-1","DOIUrl":"10.1186/s13550-024-01134-1","url":null,"abstract":"","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"74"},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035474","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 : 2024-08-13DOI: 10.1186/s13550-024-01135-0
Jordan Cheng, Joke Zink, Edward O'Neill, Bart Cornelissen, Julie Nonnekens, Lefteris Livieratos, Samantha Y A Terry
{"title":"Enhancing [<sup>177</sup>Lu]Lu-DOTA-TATE therapeutic efficacy in vitro by combining it with metronomic chemotherapeutics.","authors":"Jordan Cheng, Joke Zink, Edward O'Neill, Bart Cornelissen, Julie Nonnekens, Lefteris Livieratos, Samantha Y A Terry","doi":"10.1186/s13550-024-01135-0","DOIUrl":"10.1186/s13550-024-01135-0","url":null,"abstract":"<p><strong>Background: </strong>Peptide receptor radionuclide therapy (PRRT) uses [<sup>177</sup>Lu]Lu-[DOTA<sup>0</sup>-Tyr<sup>3</sup>]octreotate ([<sup>177</sup>Lu]Lu-DOTA-TATE) to treat patients with neuroendocrine tumours (NETs) overexpressing the somatostatin receptor 2A (SSTR2A). It has shown significant short-term improvements in survival and symptom alleviation, but there remains room for improvement. Here, we investigated whether combining [<sup>177</sup>Lu]Lu-DOTA-TATE with chemotherapeutics enhanced the in vitro therapeutic efficacy of [<sup>177</sup>Lu]Lu-DOTA-TATE.</p><p><strong>Results: </strong>Transfected human osteosarcoma (U2OS + SSTR2A, high SSTR2A expression) and pancreatic NET (BON1 + STTR2A, medium SSTR2A expression) cells were subjected to hydroxyurea, gemcitabine or triapine for 24 h at 37<sup>o</sup>C and 5% CO<sub>2</sub>. Cells were then recovered for 4 h prior to a 24-hour incubation with 0.7-1.03 MBq [<sup>177</sup>Lu]Lu-DOTA-TATE (25 nM) for uptake and metabolic viability studies. Incubation of U2OS + SSTR2A cells with hydroxyurea, gemcitabine, and triapine enhanced uptake of [<sup>177</sup>Lu]Lu-DOTA-TATE from 0.2 ± 0.1 in untreated cells to 0.4 ± 0.1, 1.1 ± 0.2, and 0.9 ± 0.2 Bq/cell in U2OS + SSTR2A cells, respectively. Cell viability post treatment with [<sup>177</sup>Lu]Lu-DOTA-TATE in cells pre-treated with chemotherapeutics was decreased compared to cells treated with [<sup>177</sup>Lu]Lu-DOTA-TATE monotherapy. For example, the viability of U2OS + SSTR2A cells incubated with [<sup>177</sup>Lu]Lu-DOTA-TATE decreased from 59.5 ± 22.3% to 18.8 ± 5.2% when pre-treated with hydroxyurea. Control conditions showed no reduced metabolic viability. Cells were also harvested to assess cell cycle progression, SSTR2A expression, and cell size by flow cytometry. Chemotherapeutics increased SSTR2A expression and cell size in U2OS + SSTR2A and BON1 + STTR2A cells. The S-phase sub-population of asynchronous U2OS + SSTR2A cell cultures was increased from 45.5 ± 3.3% to 84.8 ± 2.5%, 85.9 ± 1.9%, and 86.6 ± 2.2% when treated with hydroxyurea, gemcitabine, and triapine, respectively.</p><p><strong>Conclusions: </strong>Hydroxyurea, gemcitabine and triapine all increased cell size, SSTR2A expression, and [<sup>177</sup>Lu]Lu-DOTA-TATE uptake, whilst reducing cell metabolic viability in U2OS + SSTR2A cells when compared to [<sup>177</sup>Lu]Lu-DOTA-TATE monotherapy. Further investigations could transform patient care and positively increase outcomes for patients treated with [<sup>177</sup>Lu]Lu-DOTA-TATE.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"73"},"PeriodicalIF":3.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970893","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 impact of introducing deep learning based [<sup>18</sup>F]FDG PET denoising on EORTC and PERCIST therapeutic response assessments in digital PET/CT.","authors":"Kathleen Weyts, Justine Lequesne, Alison Johnson, Hubert Curcio, Aurélie Parzy, Elodie Coquan, Charline Lasnon","doi":"10.1186/s13550-024-01128-z","DOIUrl":"10.1186/s13550-024-01128-z","url":null,"abstract":"<p><strong>Background: </strong>[<sup>18</sup>F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [<sup>18</sup>F]FDG PET solid tumour treatment response assessments, while comparing \"standard PET\" to \"AI denoised half-duration PET\" (\"AI PET\") during follow-up.</p><p><strong>Results: </strong>110 patients referred for baseline and follow-up standard digital [<sup>18</sup>F]FDG PET/CT were prospectively included. \"Standard\" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a \"gold standard\" were compared to \"mixed\" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to \"UHD\") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTC<sub>UHD or EARL2</sub> or PERCIST<sub>UHD or EARL2</sub> mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78-0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients.</p><p><strong>Conclusions: </strong>Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [<sup>18</sup>F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"72"},"PeriodicalIF":3.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912241","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 : 2024-08-05DOI: 10.1186/s13550-024-01120-7
Zilin Wang, Yihan Tian, Yanhui Ji, Tong Liu, Shiqi Wen, Peng Wang, Jie Hu, Wei Li
{"title":"Clinical value of Tc-99m MDP SPECT/CT bone imaging for early diagnosis of Relapsing Polychondritis: a report of 5 cases.","authors":"Zilin Wang, Yihan Tian, Yanhui Ji, Tong Liu, Shiqi Wen, Peng Wang, Jie Hu, Wei Li","doi":"10.1186/s13550-024-01120-7","DOIUrl":"10.1186/s13550-024-01120-7","url":null,"abstract":"<p><strong>Background: </strong>Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient's prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases.</p><p><strong>Case presentation: </strong>These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time.</p><p><strong>Conclusions: </strong>The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"71"},"PeriodicalIF":3.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888797","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 : 2024-07-31DOI: 10.1186/s13550-024-01127-0
Kavya Prasad, Brian E Serencsits, Bae P Chu, Lawrence T Dauer, Maria Donzelli, Ellen Basu, Kim Kramer, Neeta Pandit-Taskar
{"title":"Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with <sup>131</sup>I-omburtamab for leptomeningeal disease.","authors":"Kavya Prasad, Brian E Serencsits, Bae P Chu, Lawrence T Dauer, Maria Donzelli, Ellen Basu, Kim Kramer, Neeta Pandit-Taskar","doi":"10.1186/s13550-024-01127-0","DOIUrl":"10.1186/s13550-024-01127-0","url":null,"abstract":"<p><strong>Background: </strong>Radiolabeled antibody <sup>131</sup>I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic.</p><p><strong>Methods: </strong>Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of <sup>131</sup>I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+.</p><p><strong>Results: </strong>Post-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with <sup>131</sup>I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring.</p><p><strong>Conclusion: </strong><sup>131</sup>I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"70"},"PeriodicalIF":3.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855208","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}