Pub Date : 2024-09-11DOI: 10.1007/s00259-024-06906-4
Richard Graham, David Morland, Sarah Cade, Laetitia Imbert, Emmanouil Panagiotidis, Jens Kurth, Frédéric Paycha, Tim Van den Wyngaert
The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON® and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study.
{"title":"EANM position paper on challenges and opportunities of full-ring 360° CZT bone imaging: it’s time to let go of planar whole-body bone imaging","authors":"Richard Graham, David Morland, Sarah Cade, Laetitia Imbert, Emmanouil Panagiotidis, Jens Kurth, Frédéric Paycha, Tim Van den Wyngaert","doi":"10.1007/s00259-024-06906-4","DOIUrl":"https://doi.org/10.1007/s00259-024-06906-4","url":null,"abstract":"<p>The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON<sup>®</sup> and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<h3 data-test="abstract-sub-heading">Aim</h3><p>The recently introduced Long-Axial-Field-of-View (LAFOV) PET-CT scanners allow for the first-time whole-body dynamic- and parametric imaging. Primary aim of this study was the comparison of direct and indirect Patlak imaging as well as the comparison of different time frames for Patlak calculation with the LAFOV PET-CT in oncological patients. Secondary aims of the study were lesion detectability and comparison of Patlak analysis with a two-tissue-compartment model (2TCM).</p><h3 data-test="abstract-sub-heading">Methodology</h3><p>50 oncological patients with 346 tumor lesions were enrolled in the study. All patients underwent [<sup>18</sup>F]FDG PET/CT (skull to upper thigh). Here, the Image-Derived-Input-Function) (IDIF) from the descending aorta was used as the exclusive input function. Four sets of images have been reviewed visually and evaluated quantitatively using the target-to-background (TBR) and contrast-to-noise ratio (CNR): short-time (30 min)-direct (STD) Patlak K<sub>i</sub>, short-time (30 min)-indirect (STI) Patlak K<sub>i</sub>, long-time (59.25 min)-indirect (LTI) Patlak K<sub>i</sub>, and 50–60 min SUV (sumSUV). VOI-based 2TCM was used for the evaluation of tumor lesions and normal tissues and compared with the results of Patlak model.</p><h3 data-test="abstract-sub-heading">Results</h3><p>No significant differences were observed between the four approaches regarding the number of tumor lesions. However, we found three discordant results: a true positive liver lesion in all Patlak K<sub>i</sub> images, a false positive liver lesion delineated only in LTI K<sub>i</sub> which was a hemangioma according to MRI and a true negative example in a patient with an atelectasis next to a lung tumor. STD, STI and LTI K<sub>i</sub> images had superior TBR in comparison with sumSUV images (2.9-, 3.3- and 4.3-fold higher respectively). TBR of LTI K<sub>i</sub> were significantly higher than STD K<sub>i</sub>. VOI-based k<sub>3</sub> showed a 21-fold higher TBR than sumSUV. Parameters of different models vary in their differential capability between tumor lesions and normal tissue like Patlak K<sub>i</sub> which was better in normal lung and 2TCM k<sub>3</sub> which was better in normal liver. 2TCM K<sub>i</sub> revealed the highest correlation (<i>r</i> = 0.95) with the LTI Patlak K<sub>i</sub> in tumor lesions group and demonstrated the highest correlation with the STD Patlak K<sub>i</sub> in all tissues group and normal tissues group (<i>r</i> = 0.93 and <i>r</i> = 0.74 respectively).</p><h3 data-test="abstract-sub-heading">Conclusions</h3><p>Dynamic [<sup>18</sup>F]-FDG with the new LAFOV PET/CT scanner produces Patlak K<sub>i</sub> images with better lesion contrast than SUV images, but does not increase the lesion detection rate. The time window used for Patlak imaging plays a more important role than the direct or indirect method. A combination of different models, like Patlak and 2TCM may
最近推出的长轴视野（LAFOV）PET-CT 扫描仪首次实现了全身动态和参数成像。本研究的主要目的是比较直接和间接 Patlak 成像，以及比较使用 LAFOV PET-CT 对肿瘤患者进行 Patlak 计算的不同时间框架。研究的次要目的是病灶的可探测性以及将 Patlak 分析与双组织室模型 (2TCM) 进行比较。所有患者都接受了[18F]FDG PET/CT（从头颅到大腿上部）检查。在此，降主动脉的图像衍生输入函数（IDIF）被用作唯一的输入函数。对四组图像进行了直观审查，并使用目标-背景（TBR）和对比-噪声比（CNR）进行了定量评估：短时间（30 分钟）-直接（STD）Patlak Ki、短时间（30 分钟）-间接（STI）Patlak Ki、长时间（59.25 分钟）-间接（LTI）Patlak Ki 和 50-60 分钟 SUV（sumSUV）。基于 VOI 的 2TCM 用于评估肿瘤病灶和正常组织，并与 Patlak 模型的结果进行比较。然而，我们发现了三个不一致的结果：在所有 Patlak Ki 图像中都有一个真阳性肝脏病变，只有 LTI Ki 中才有一个假阳性肝脏病变，而根据核磁共振成像，该肝脏病变是一个血管瘤，还有一个真阴性病例，患者肺部肿瘤旁有一个肺大泡。STD、STI 和 LTI Ki 图像的 TBR 高于 sumSUV 图像（分别高出 2.9 倍、3.3 倍和 4.3 倍）。LTI Ki 的 TBR 明显高于 STD Ki。基于 VOI 的 k3 的 TBR 比 sumSUV 高 21 倍。不同模型的参数在肿瘤病变和正常组织之间的差异能力各不相同，如 Patlak Ki 在正常肺部的差异能力更强，而 2TCM k3 在正常肝脏的差异能力更强。在肿瘤病变组中，2TCM Ki 与 LTI Patlak Ki 的相关性最高（r = 0.95），在所有组织组和正常组织组中，2TCM Ki 与 STD Patlak Ki 的相关性最高（r = 0.93 和 r = 0.74）。与直接或间接方法相比，Patlak 成像所用的时间窗起着更重要的作用。不同模型（如 Patlak 和 2TCM）的组合可能有助于参数成像，从而在未来获得全身最佳的 TBR。
{"title":"Impact of different parametric Patlak imaging approaches and comparison with a 2-tissue compartment pharmacokinetic model with a long axial field-of-view (LAFOV) PET/CT in oncological patients","authors":"Leyun Pan, Christos Sachpekidis, Jessica Hassel, Petros Christopoulos, Antonia Dimitrakopoulou-Strauss","doi":"10.1007/s00259-024-06879-4","DOIUrl":"https://doi.org/10.1007/s00259-024-06879-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aim</h3><p>The recently introduced Long-Axial-Field-of-View (LAFOV) PET-CT scanners allow for the first-time whole-body dynamic- and parametric imaging. Primary aim of this study was the comparison of direct and indirect Patlak imaging as well as the comparison of different time frames for Patlak calculation with the LAFOV PET-CT in oncological patients. Secondary aims of the study were lesion detectability and comparison of Patlak analysis with a two-tissue-compartment model (2TCM).</p><h3 data-test=\"abstract-sub-heading\">Methodology</h3><p>50 oncological patients with 346 tumor lesions were enrolled in the study. All patients underwent [<sup>18</sup>F]FDG PET/CT (skull to upper thigh). Here, the Image-Derived-Input-Function) (IDIF) from the descending aorta was used as the exclusive input function. Four sets of images have been reviewed visually and evaluated quantitatively using the target-to-background (TBR) and contrast-to-noise ratio (CNR): short-time (30 min)-direct (STD) Patlak K<sub>i</sub>, short-time (30 min)-indirect (STI) Patlak K<sub>i</sub>, long-time (59.25 min)-indirect (LTI) Patlak K<sub>i</sub>, and 50–60 min SUV (sumSUV). VOI-based 2TCM was used for the evaluation of tumor lesions and normal tissues and compared with the results of Patlak model.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>No significant differences were observed between the four approaches regarding the number of tumor lesions. However, we found three discordant results: a true positive liver lesion in all Patlak K<sub>i</sub> images, a false positive liver lesion delineated only in LTI K<sub>i</sub> which was a hemangioma according to MRI and a true negative example in a patient with an atelectasis next to a lung tumor. STD, STI and LTI K<sub>i</sub> images had superior TBR in comparison with sumSUV images (2.9-, 3.3- and 4.3-fold higher respectively). TBR of LTI K<sub>i</sub> were significantly higher than STD K<sub>i</sub>. VOI-based k<sub>3</sub> showed a 21-fold higher TBR than sumSUV. Parameters of different models vary in their differential capability between tumor lesions and normal tissue like Patlak K<sub>i</sub> which was better in normal lung and 2TCM k<sub>3</sub> which was better in normal liver. 2TCM K<sub>i</sub> revealed the highest correlation (<i>r</i> = 0.95) with the LTI Patlak K<sub>i</sub> in tumor lesions group and demonstrated the highest correlation with the STD Patlak K<sub>i</sub> in all tissues group and normal tissues group (<i>r</i> = 0.93 and <i>r</i> = 0.74 respectively).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Dynamic [<sup>18</sup>F]-FDG with the new LAFOV PET/CT scanner produces Patlak K<sub>i</sub> images with better lesion contrast than SUV images, but does not increase the lesion detection rate. The time window used for Patlak imaging plays a more important role than the direct or indirect method. A combination of different models, like Patlak and 2TCM may","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1007/s00259-024-06917-1
Liu Yang, Ping Dong, Li Li, Lin Li, Minggang Su
{"title":"Positive amyloid and tau PET in an early-onset Alzheimer's disease with a rare PSEN1 (Arg278Gly) mutation.","authors":"Liu Yang, Ping Dong, Li Li, Lin Li, Minggang Su","doi":"10.1007/s00259-024-06917-1","DOIUrl":"https://doi.org/10.1007/s00259-024-06917-1","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1007/s00259-024-06910-8
Dongsheng Xu, You Zhang, Wei Huang, Xinbing Pan, Shuxian An, Cheng Wang, Gang Huang, Jianjun Liu, Weijun Wei
Purpose: Epithelial cell adhesion molecule (EpCAM) is a potential therapeutic target and anchoring molecule for circulating and disseminated tumour cells (CTC/DTC) in liquid biopsy. In this study, we aimed to construct EpCAM-specific immuno-positron emission tomography (immunoPET) imaging probes and assess the diagnostic abilities in preclinical cancer models.
Methods: By engineering six single-domain antibodies (e.g., EPCD1 - 6) targeting EpCAM of different binding properties and labelling with 68Ga (T1/2 = 1.1 h) and 18F (T1/2 = 110 min), we developed a series of EpCAM-targeted immunoPET imaging probes. The probes' pharmacokinetics and diagnostic accuracies were investigated in cell-derived human colorectal (LS174T) and esophageal cancer (OE19) tumour models.
Results: Based on in vitro binding affinities and in vivo pharmacokinetics of the first three tracers ([68Ga]Ga-NOTA-EPCD1, [68Ga]Ga-NOTA-EPCD2, and [68Ga]Ga-NOTA-EPCD3), we selected [68Ga]Ga-NOTA-EPCD3 for tumour imaging which showed an average tumour uptake of 2.06 ± 0.124%ID/g (n = 3) in LS174T cell-derived tumour model. Development and characterisation of [18F]AIF-RESCA-EPCD3 showed comparable tumour uptake of 1.73 ± 0.0471%ID/g (n = 3) in the same tumour model. Further validation of [68Ga]Ga-NOTA-EPCD3 in OE19 cell-derived tumour model showed an average tumour uptake of 4.27 ± 1.16%ID/g and liver uptake of 13.5 ± 1.30%ID/g (n = 3). Near-infrared fluorescence imaging with Cy7-EPCD3 confirmed the in vivo pharmacokinetics and relatively high liver accumulation. We further synthesized another three 18F-labeled nanobody tracers ([18F]AIF-RESCA-EPCD4, [18F]AIF-RESCA-EPCD5, and [18F]AIF-RESCA-EPCD6) and found that [18F]AIF-RESCA-EPCD6 had the best pharmacokinetics with low background. [18F]AIF-RESCA-EPCD6 showed explicit uptake in the subcutaneously inoculated OE19 tumour model with an average uptake of 4.70 ± 0.26%ID/g (n = 3). In comparison, the corresponding tumour uptake (0.17 ± 0.25%ID/g, n = 3) in the EPCD6 blocking group was substantially lower (P < 0.001), indicating the targeting specificity of the tracer.
Conclusions: We developed a series of 68Ga/18F-labeled nanobody tracers targeting human EpCAM. ImmunoPET imaging with [18F]AIF-RESCA-EPCD6 may facilitate better use of EpCAM-targeted therapeutics by noninvasively displaying the target's expression dynamics.
{"title":"ImmunoPET imaging of EpCAM in solid tumours with nanobody tracers: a preclinical study.","authors":"Dongsheng Xu, You Zhang, Wei Huang, Xinbing Pan, Shuxian An, Cheng Wang, Gang Huang, Jianjun Liu, Weijun Wei","doi":"10.1007/s00259-024-06910-8","DOIUrl":"https://doi.org/10.1007/s00259-024-06910-8","url":null,"abstract":"<p><strong>Purpose: </strong>Epithelial cell adhesion molecule (EpCAM) is a potential therapeutic target and anchoring molecule for circulating and disseminated tumour cells (CTC/DTC) in liquid biopsy. In this study, we aimed to construct EpCAM-specific immuno-positron emission tomography (immunoPET) imaging probes and assess the diagnostic abilities in preclinical cancer models.</p><p><strong>Methods: </strong>By engineering six single-domain antibodies (e.g., EPCD1 - 6) targeting EpCAM of different binding properties and labelling with <sup>68</sup>Ga (T<sub>1/2</sub> = 1.1 h) and <sup>18</sup>F (T<sub>1/2</sub> = 110 min), we developed a series of EpCAM-targeted immunoPET imaging probes. The probes' pharmacokinetics and diagnostic accuracies were investigated in cell-derived human colorectal (LS174T) and esophageal cancer (OE19) tumour models.</p><p><strong>Results: </strong>Based on in vitro binding affinities and in vivo pharmacokinetics of the first three tracers ([<sup>68</sup>Ga]Ga-NOTA-EPCD1, [<sup>68</sup>Ga]Ga-NOTA-EPCD2, and [<sup>68</sup>Ga]Ga-NOTA-EPCD3), we selected [<sup>68</sup>Ga]Ga-NOTA-EPCD3 for tumour imaging which showed an average tumour uptake of 2.06 ± 0.124%ID/g (n = 3) in LS174T cell-derived tumour model. Development and characterisation of [<sup>18</sup>F]AIF-RESCA-EPCD3 showed comparable tumour uptake of 1.73 ± 0.0471%ID/g (n = 3) in the same tumour model. Further validation of [<sup>68</sup>Ga]Ga-NOTA-EPCD3 in OE19 cell-derived tumour model showed an average tumour uptake of 4.27 ± 1.16%ID/g and liver uptake of 13.5 ± 1.30%ID/g (n = 3). Near-infrared fluorescence imaging with Cy7-EPCD3 confirmed the in vivo pharmacokinetics and relatively high liver accumulation. We further synthesized another three <sup>18</sup>F-labeled nanobody tracers ([<sup>18</sup>F]AIF-RESCA-EPCD4, [<sup>18</sup>F]AIF-RESCA-EPCD5, and [<sup>18</sup>F]AIF-RESCA-EPCD6) and found that [<sup>18</sup>F]AIF-RESCA-EPCD6 had the best pharmacokinetics with low background. [<sup>18</sup>F]AIF-RESCA-EPCD6 showed explicit uptake in the subcutaneously inoculated OE19 tumour model with an average uptake of 4.70 ± 0.26%ID/g (n = 3). In comparison, the corresponding tumour uptake (0.17 ± 0.25%ID/g, n = 3) in the EPCD6 blocking group was substantially lower (P < 0.001), indicating the targeting specificity of the tracer.</p><p><strong>Conclusions: </strong>We developed a series of <sup>68</sup>Ga/<sup>18</sup>F-labeled nanobody tracers targeting human EpCAM. ImmunoPET imaging with [<sup>18</sup>F]AIF-RESCA-EPCD6 may facilitate better use of EpCAM-targeted therapeutics by noninvasively displaying the target's expression dynamics.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1007/s00259-024-06914-4
Hannelore Ceuppens, Ana Rita Pombo Antunes, Laurent Navarro, Thomas Ertveldt, Marion Berdal, Surasa Nagachinta, Kirsten De Ridder, Tony Lahoutte, Marleen Keyaerts, Nick Devoogdt, Cleo Goyvaerts, Matthias D'Huyvetter, Karine Breckpot
Purpose: Targeted radionuclide therapy (TRT) is a cancer treatment with relative therapeutic efficacy across various cancer types. We studied the therapeutic potential of TRT using fibroblast activation protein-α (FAP) targeting sdAbs (4AH29) labelled with 225Ac or 131I in immunocompetent mice in a human FAP (hFAP) expressing lung cancer mouse model. We further explored the combination of TRT with programmed cell death ligand 1 (PD-L1) immune checkpoint blockade (ICB).
Methods: We studied the biodistribution and tumour uptake of [131I]I-GMIB-4AH29 and [225Ac]Ac-DOTA-4AH29 by ex vivo γ-counting. Therapeutic efficacy of [131I]I-GMIB-4AH29 and [225Ac]Ac-DOTA-4AH29 was evaluated in an immunocompetent mouse model. Flow cytometry analysis of tumours from [225Ac]Ac-DOTA-4AH29 treated mice was performed. Treatment with [225Ac]Ac-DOTA-4AH29 was repeated in combination with PD-L1 ICB.
Results: The biodistribution showed high tumour uptake of [131I]I-GMIB-4AH29 with 3.5 ± 0.5% IA/g 1 h post-injection (p.i.) decreasing to 0.9 ± 0.1% IA/g after 24 h. Tumour uptake of [225Ac]Ac-DOTA-4AH29 was also relevant with 2.1 ± 0.5% IA/g 1 h p.i. with a less steep decrease to 1.7 ± 0.2% IA/g after 24 h. Survival was significantly improved after treatment with low and high doses [131I]I-GMIB-4AH29 or [225Ac]Ac-DOTA-4AH29 compared to vehicle solution. Moreover, we observed significantly higher PD-L1 expression in tumours of mice treated with [225Ac]Ac-DOTA-4AH29 compared to vehicle solution. Therefore, we combined high dose [225Ac]Ac-DOTA-4AH29 with PD-L1 ICB showing therapeutic synergy.
Conclusion: [225Ac]Ac-DOTA-4AH29 and [131I]I-GMIB-4AH29 exhibit high and persistent tumour targeting, translating into prolonged survival in mice bearing aggressive tumours. Moreover, we demonstrate that the combination of PD-L1 ICB with [225Ac]Ac-DOTA-4AH29 TRT enhances its therapeutic efficacy.
{"title":"Efficient α and β<sup>-</sup> radionuclide therapy targeting fibroblast activation protein-α in an aggressive preclinical mouse tumour model.","authors":"Hannelore Ceuppens, Ana Rita Pombo Antunes, Laurent Navarro, Thomas Ertveldt, Marion Berdal, Surasa Nagachinta, Kirsten De Ridder, Tony Lahoutte, Marleen Keyaerts, Nick Devoogdt, Cleo Goyvaerts, Matthias D'Huyvetter, Karine Breckpot","doi":"10.1007/s00259-024-06914-4","DOIUrl":"https://doi.org/10.1007/s00259-024-06914-4","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted radionuclide therapy (TRT) is a cancer treatment with relative therapeutic efficacy across various cancer types. We studied the therapeutic potential of TRT using fibroblast activation protein-α (FAP) targeting sdAbs (4AH29) labelled with <sup>225</sup>Ac or <sup>131</sup>I in immunocompetent mice in a human FAP (hFAP) expressing lung cancer mouse model. We further explored the combination of TRT with programmed cell death ligand 1 (PD-L1) immune checkpoint blockade (ICB).</p><p><strong>Methods: </strong>We studied the biodistribution and tumour uptake of [<sup>131</sup>I]I-GMIB-4AH29 and [<sup>225</sup>Ac]Ac-DOTA-4AH29 by ex vivo γ-counting. Therapeutic efficacy of [<sup>131</sup>I]I-GMIB-4AH29 and [<sup>225</sup>Ac]Ac-DOTA-4AH29 was evaluated in an immunocompetent mouse model. Flow cytometry analysis of tumours from [<sup>225</sup>Ac]Ac-DOTA-4AH29 treated mice was performed. Treatment with [<sup>225</sup>Ac]Ac-DOTA-4AH29 was repeated in combination with PD-L1 ICB.</p><p><strong>Results: </strong>The biodistribution showed high tumour uptake of [<sup>131</sup>I]I-GMIB-4AH29 with 3.5 ± 0.5% IA/g 1 h post-injection (p.i.) decreasing to 0.9 ± 0.1% IA/g after 24 h. Tumour uptake of [<sup>225</sup>Ac]Ac-DOTA-4AH29 was also relevant with 2.1 ± 0.5% IA/g 1 h p.i. with a less steep decrease to 1.7 ± 0.2% IA/g after 24 h. Survival was significantly improved after treatment with low and high doses [<sup>131</sup>I]I-GMIB-4AH29 or [<sup>225</sup>Ac]Ac-DOTA-4AH29 compared to vehicle solution. Moreover, we observed significantly higher PD-L1 expression in tumours of mice treated with [<sup>225</sup>Ac]Ac-DOTA-4AH29 compared to vehicle solution. Therefore, we combined high dose [<sup>225</sup>Ac]Ac-DOTA-4AH29 with PD-L1 ICB showing therapeutic synergy.</p><p><strong>Conclusion: </strong>[<sup>225</sup>Ac]Ac-DOTA-4AH29 and [<sup>131</sup>I]I-GMIB-4AH29 exhibit high and persistent tumour targeting, translating into prolonged survival in mice bearing aggressive tumours. Moreover, we demonstrate that the combination of PD-L1 ICB with [<sup>225</sup>Ac]Ac-DOTA-4AH29 TRT enhances its therapeutic efficacy.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1007/s00259-024-06863-y
Marco Maccauro, Mariarosaria Cuomo, Matteo Bauckneht, Matteo Bagnalasta, Stefania Mazzaglia, Federica Scalorbi, Giovanni Argiroffi, Margarita Kirienko, Alice Lorenzoni, Gianluca Aliberti, Sara Pusceddu, Calareso Giuseppina, Garanzini Enrico Matteo, Ettore Seregni, Carlo Chiesa
<p><strong>Purpose: </strong>In Peptide Receptor Radionuclide Therapy (PRRT) with [<sup>177</sup>Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [<sup>177</sup>Lu]Lu-DOTATATE therapeutic regimen.</p><p><strong>Methods: </strong>The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18-45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months.</p><p><strong>Results: </strong>The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD_1 and GTD_TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD_1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 - 37]). Using GTD_TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD_1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD_1.</p><p><strong>Discussion: </strong>Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of <sup>177</sup>Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m).</p><p><strong>Conclusion: </strong>Tumour dosimetry after the first adminis
{"title":"The LUTADOSE trial: tumour dosimetry after the first administration predicts progression free survival in gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) patients treated with [<sup>177</sup>Lu]Lu-DOTATATE.","authors":"Marco Maccauro, Mariarosaria Cuomo, Matteo Bauckneht, Matteo Bagnalasta, Stefania Mazzaglia, Federica Scalorbi, Giovanni Argiroffi, Margarita Kirienko, Alice Lorenzoni, Gianluca Aliberti, Sara Pusceddu, Calareso Giuseppina, Garanzini Enrico Matteo, Ettore Seregni, Carlo Chiesa","doi":"10.1007/s00259-024-06863-y","DOIUrl":"https://doi.org/10.1007/s00259-024-06863-y","url":null,"abstract":"<p><strong>Purpose: </strong>In Peptide Receptor Radionuclide Therapy (PRRT) with [<sup>177</sup>Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [<sup>177</sup>Lu]Lu-DOTATATE therapeutic regimen.</p><p><strong>Methods: </strong>The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18-45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months.</p><p><strong>Results: </strong>The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD_1 and GTD_TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD_1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 - 37]). Using GTD_TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD_1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD_1.</p><p><strong>Discussion: </strong>Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of <sup>177</sup>Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m).</p><p><strong>Conclusion: </strong>Tumour dosimetry after the first adminis","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1007/s00259-024-06895-4
Martin Freesmeyer, Julia Greiser, Robert Drescher, Utz Settmacher, Oliver Rohland, Felix Dondorf
{"title":"PET/CT with [<sup>68</sup>Ga]Ga-TEoS-DAZA for localization of a traumatic biliary leak.","authors":"Martin Freesmeyer, Julia Greiser, Robert Drescher, Utz Settmacher, Oliver Rohland, Felix Dondorf","doi":"10.1007/s00259-024-06895-4","DOIUrl":"https://doi.org/10.1007/s00259-024-06895-4","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1007/s00259-024-06900-w
Gaetan Devos, Alexander Giesen, Steven Joniau
{"title":"Refining salvage radiotherapy strategies for pelvic node recurrence in prostate cancer: insights from salvage lymph node dissection.","authors":"Gaetan Devos, Alexander Giesen, Steven Joniau","doi":"10.1007/s00259-024-06900-w","DOIUrl":"https://doi.org/10.1007/s00259-024-06900-w","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI).
Materials and methods: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner.
Results: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice.
Conclusions: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.
{"title":"Non-invasive diagnosis of liver fibrosis via MRI using targeted gadolinium-based nanoparticles.","authors":"Shiman Wu, Tingting Xu, Jiahao Gao, Qi Zhang, Yuxin Huang, Zonglin Liu, Xiaozhu Hao, Zhenwei Yao, Xing Hao, Pu-Yeh Wu, Yue Wu, Bo Yin, Zhongmin Tang","doi":"10.1007/s00259-024-06894-5","DOIUrl":"https://doi.org/10.1007/s00259-024-06894-5","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI).</p><p><strong>Materials and methods: </strong>NaGdF<sub>4</sub> nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF<sub>4</sub>@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF<sub>4</sub>@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF<sub>4</sub>@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner.</p><p><strong>Results: </strong>NaGdF<sub>4</sub>@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF<sub>4</sub>@PEG@HA nanoprobes by JS1 cells compared to NaGdF<sub>4</sub>@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF<sub>4</sub>@PEG@HA. NaGdF<sub>4</sub>@PEG@HA demonstrated higher targeting ability in fibrotic mice.</p><p><strong>Conclusions: </strong>NaGdF<sub>4</sub>@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.</p>","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1007/s00259-024-06909-1
Masatoshi Hotta, Ameen Seyedroudbari, Sarah Dry, Mark Girgis, Jeremie Calais
{"title":"Characterization of a gonadal vein Capillary Hemangioma by [68Ga]FAPI-46 and [18 F]FDG PET and immunohistochemistry: a potential pitfall of FAPI PET signal.","authors":"Masatoshi Hotta, Ameen Seyedroudbari, Sarah Dry, Mark Girgis, Jeremie Calais","doi":"10.1007/s00259-024-06909-1","DOIUrl":"https://doi.org/10.1007/s00259-024-06909-1","url":null,"abstract":"","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号