Theodorus J P Jansen, Sevilay Tokgöz, Mijke Buitinga, Sanne A M van Lith, Lieke Joosten, Cathelijne Frielink, Esther M M Smeets, Martijn W J Stommel, Marion B van der Kolk, Bastiaan E de Galan, Maarten Brom, Marti Boss, Martin Gotthardt
{"title":"通过人体胰腺体外自显影和免疫组化技术验证用于β细胞成像的放射性标记外显素。","authors":"Theodorus J P Jansen, Sevilay Tokgöz, Mijke Buitinga, Sanne A M van Lith, Lieke Joosten, Cathelijne Frielink, Esther M M Smeets, Martijn W J Stommel, Marion B van der Kolk, Bastiaan E de Galan, Maarten Brom, Marti Boss, Martin Gotthardt","doi":"10.1186/s13550-024-01159-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with <sup>111</sup>In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of <sup>111</sup>In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo RESULTS: Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.</p><p><strong>Conclusion: </strong>Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .</p><p><strong>Clinicaltrials: </strong>gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480297/pdf/","citationCount":"0","resultStr":"{\"title\":\"Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas.\",\"authors\":\"Theodorus J P Jansen, Sevilay Tokgöz, Mijke Buitinga, Sanne A M van Lith, Lieke Joosten, Cathelijne Frielink, Esther M M Smeets, Martijn W J Stommel, Marion B van der Kolk, Bastiaan E de Galan, Maarten Brom, Marti Boss, Martin Gotthardt\",\"doi\":\"10.1186/s13550-024-01159-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with <sup>111</sup>In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of <sup>111</sup>In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo RESULTS: Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.</p><p><strong>Conclusion: </strong>Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .</p><p><strong>Clinicaltrials: </strong>gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .</p>\",\"PeriodicalId\":11611,\"journal\":{\"name\":\"EJNMMI Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480297/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01159-6\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13550-024-01159-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas.
Background: Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with 111In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of 111In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo RESULTS: Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.
Conclusion: Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.
EJNMMI ResearchRADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍：
EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies.
The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
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