Daniel Johnathan Hughes, Gitasha Chand, Jessica Johnson, Ronan Tegala, Damion Bailey, Kathryn Adamson, Scott Edmonds, Levente K Meszaros, Amelia Elizabeth Broomfield Moore, Thubeena Manickavasagar, Susan Ndagire, Spyridon Gennatas, Alexandros Georgiou, Sharmistha Ghosh, Debra Josephs, Eleni Karapanagiotou, Emma McLean, Hong Hoi Ting, James Spicer, Vicky Goh, Gary J R Cook
{"title":"[99mTc]NM-01 SPECT/CT PD-L1成像与晚期肺癌伴/不伴化疗派姆单抗的代谢反应相关。","authors":"Daniel Johnathan Hughes, Gitasha Chand, Jessica Johnson, Ronan Tegala, Damion Bailey, Kathryn Adamson, Scott Edmonds, Levente K Meszaros, Amelia Elizabeth Broomfield Moore, Thubeena Manickavasagar, Susan Ndagire, Spyridon Gennatas, Alexandros Georgiou, Sharmistha Ghosh, Debra Josephs, Eleni Karapanagiotou, Emma McLean, Hong Hoi Ting, James Spicer, Vicky Goh, Gary J R Cook","doi":"10.1038/s41416-025-02991-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [<sup>99m</sup>Tc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.</p><p><strong>Methods: </strong>PD-L1 tumour proportion score (TPS) measured using SP263 assay. [<sup>99m</sup>Tc]NM-01 SPECT/CT and [<sup>18</sup>F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROI<sub>max</sub>) measurements performed in primary and metastatic lesions using SPECT/CT images.</p><p><strong>Results: </strong>Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [<sup>99m</sup>Tc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [<sup>18</sup>F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [<sup>99m</sup>Tc]NM-01 T:BP (r = -0.73, p < 0.05), but only moderately with PD-L1 TPS (r = -0.46, p = 0.06).</p><p><strong>Conclusion: </strong>[<sup>99m</sup>Tc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [<sup>99m</sup>Tc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.</p><p><strong>Clinical trials registration: </strong>PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PD-L1 imaging with [<sup>99m</sup>Tc]NM-01 SPECT/CT is associated with metabolic response to pembrolizumab with/without chemotherapy in advanced lung cancer.\",\"authors\":\"Daniel Johnathan Hughes, Gitasha Chand, Jessica Johnson, Ronan Tegala, Damion Bailey, Kathryn Adamson, Scott Edmonds, Levente K Meszaros, Amelia Elizabeth Broomfield Moore, Thubeena Manickavasagar, Susan Ndagire, Spyridon Gennatas, Alexandros Georgiou, Sharmistha Ghosh, Debra Josephs, Eleni Karapanagiotou, Emma McLean, Hong Hoi Ting, James Spicer, Vicky Goh, Gary J R Cook\",\"doi\":\"10.1038/s41416-025-02991-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [<sup>99m</sup>Tc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.</p><p><strong>Methods: </strong>PD-L1 tumour proportion score (TPS) measured using SP263 assay. [<sup>99m</sup>Tc]NM-01 SPECT/CT and [<sup>18</sup>F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROI<sub>max</sub>) measurements performed in primary and metastatic lesions using SPECT/CT images.</p><p><strong>Results: </strong>Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [<sup>99m</sup>Tc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [<sup>18</sup>F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [<sup>99m</sup>Tc]NM-01 T:BP (r = -0.73, p < 0.05), but only moderately with PD-L1 TPS (r = -0.46, p = 0.06).</p><p><strong>Conclusion: </strong>[<sup>99m</sup>Tc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [<sup>99m</sup>Tc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.</p><p><strong>Clinical trials registration: </strong>PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406.</p>\",\"PeriodicalId\":9243,\"journal\":{\"name\":\"British Journal of Cancer\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41416-025-02991-w\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41416-025-02991-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
PD-L1 imaging with [99mTc]NM-01 SPECT/CT is associated with metabolic response to pembrolizumab with/without chemotherapy in advanced lung cancer.
Background: Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [99mTc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.
Methods: PD-L1 tumour proportion score (TPS) measured using SP263 assay. [99mTc]NM-01 SPECT/CT and [18F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROImax) measurements performed in primary and metastatic lesions using SPECT/CT images.
Results: Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [99mTc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [18F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [99mTc]NM-01 T:BP (r = -0.73, p < 0.05), but only moderately with PD-L1 TPS (r = -0.46, p = 0.06).
Conclusion: [99mTc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [99mTc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.
Clinical trials registration: PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406.
期刊介绍：
The British Journal of Cancer is one of the most-cited general cancer journals, publishing significant advances in translational and clinical cancer research.It also publishes high-quality reviews and thought-provoking comment on all aspects of cancer prevention,diagnosis and treatment.
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