{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:36:03Z","timestamp":1783632963120,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","award":["YING"],"award-info":[{"award-number":["YING"]}],"id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer 68Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard 18F-FDG PET\/computed tomography (CT). In our database, we retrospectively identified 11 treatment-na\u00efve patients with histologically proven NEC, who underwent 18F-FDG and CXCR4-directed PET\/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. 68Ga-Pentixafor visualized tumor lesions in 10\/11 subjects, while18F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10\/11 cases, 18F-FDG PET\/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p &lt; 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to 68Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 \u00b1 9.8 vs. 5.2 \u00b1 3.7; SUVmean: 7.4 \u00b1 5.4 vs. 3.1 \u00b1 3.2, p &lt; 0.001; and, TBR 7.2 \u00b1 7.9 vs. 3.4 \u00b1 3.0, p &lt; 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard 18F-FDG PET\/CT.<\/jats:p>","DOI":"10.3390\/diagnostics11040605","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T04:29:14Z","timestamp":1616992154000},"page":"605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["CXCR4-Directed PET\/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-1347","authenticated-orcid":false,"given":"Alexander","family":"Weich","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf A.","family":"Werner","sequence":"additional","affiliation":[{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas K.","family":"Buck","sequence":"additional","affiliation":[{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-9849","authenticated-orcid":false,"given":"Philipp E.","family":"Hartrampf","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian E.","family":"Serfling","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scheurlen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-J\u00fcrgen","family":"Wester","sequence":"additional","affiliation":[{"name":"Pharmaceutical Radiochemistry, Technische Universit\u00e4t M\u00fcnchen, 80333 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Meining","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Gastroenterology, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kircher","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan"},{"name":"Comprehensive Heart Failure Center, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Pomper","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Rowe","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-2207","authenticated-orcid":false,"given":"Constantin","family":"Lapa","sequence":"additional","affiliation":[{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Nuclear Medicine, Medical Faculty, University of Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-0881","authenticated-orcid":false,"given":"Malte","family":"Kircher","sequence":"additional","affiliation":[{"name":"European Neuroendocrine Tumor Society (ENETS) Center of Excellence, NET Zentrum, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Department of Nuclear Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Nuclear Medicine, Medical Faculty, University of Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1097\/MPA.0b013e3181ec124e","article-title":"The pathologic classification of neuroendocrine tumors: A review of nomenclature, grading, and staging systems","volume":"39","author":"Klimstra","year":"2010","journal-title":"Pancreas"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1159\/000443168","article-title":"ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms","volume":"103","author":"Sundin","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1200\/JCO.2018.78.5865","article-title":"Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With (177)Lu-Dotatate in the Phase III NETTER-1 Trial","volume":"36","author":"Strosberg","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.7150\/thno.13702","article-title":"[(177)Lu-DOTA](0)-D-Phe(1)-Tyr(3)-Octreotide ((177)Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study","volume":"6","author":"Baum","year":"2016","journal-title":"Theranostics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","article-title":"Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Pavel","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/ERC-18-0424","article-title":"Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: A multicenter cohort study","volume":"26","author":"Carlsen","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.2967\/jnumed.118.215848","article-title":"Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients","volume":"60","author":"Zhang","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s00259-017-3821-2","article-title":"Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN)\u2014A single-institution retrospective analysis","volume":"45","author":"Thang","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000454761","article-title":"Neuroendocrine Cancer, Therapeutic Strategies in G3 Cancers","volume":"95","author":"Rinke","year":"2017","journal-title":"Digestion"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.7150\/thno.18068","article-title":"Dual Somatostatin Receptor\/FDG PET\/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance","volume":"7","author":"Chan","year":"2017","journal-title":"Theranostics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27566","DOI":"10.18632\/oncotarget.4491","article-title":"Inverse expression of somatostatin and CXCR4 chemokine receptors in gastroenteropancreatic neuroendocrine neoplasms of different malignancy","volume":"6","author":"Kaemmerer","year":"2015","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.7150\/thno.18754","article-title":"Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors\u2014A Triple Tracer Comparative Approach","volume":"7","author":"Werner","year":"2017","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"248","DOI":"10.2967\/jnumed.115.167361","article-title":"First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease","volume":"57","author":"Herrmann","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.7150\/thno.19050","article-title":"CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed Multiple Myeloma","volume":"7","author":"Lapa","year":"2017","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2967\/jnumed.118.210997","article-title":"Feasibility of CXCR4-Directed Radioligand Therapy in Advanced Diffuse Large B-Cell Lymphoma","volume":"60","author":"Lapa","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.nucmedbio.2013.09.002","article-title":"Cationic eluate pretreatment for automated synthesis of [\u2076\u2078Ga]CPCR4.2","volume":"41","author":"Martin","year":"2014","journal-title":"Nucl. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2967\/jnumed.115.161034","article-title":"First Experience with Chemokine Receptor CXCR4-Targeted PET Imaging of Patients with Solid Cancers","volume":"57","author":"Vag","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"770","DOI":"10.3389\/fonc.2019.00770","article-title":"CXCR4-Directed Imaging in Solid Tumors","volume":"9","author":"Werner","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2967\/jnumed.118.223420","article-title":"Side Effects of CXC-Chemokine Receptor 4-Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation","volume":"60","author":"Maurer","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40644-021-00391-w","article-title":"Pentixafor PET\/CT for imaging of chemokine receptor 4 expression in esophageal cancer\u2014A first clinical approach","volume":"21","author":"Linde","year":"2021","journal-title":"Cancer Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3389\/fonc.2019.00503","article-title":"[(68)Ga]-Pentixafor PET\/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas","volume":"9","author":"Breun","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8264","DOI":"10.7150\/thno.45537","article-title":"A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency","volume":"10","author":"Osl","year":"2020","journal-title":"Theranostics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"951","DOI":"10.2967\/jnumed.119.240440","article-title":"The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care Toward Molecular Medicine","volume":"61","author":"Werner","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18865","DOI":"10.18632\/oncotarget.7738","article-title":"CXCR4\/CXCL12\/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR","volume":"7","author":"Circelli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/bjh.15096","article-title":"Potential influence of concomitant chemotherapy on CXCR4 expression in receptor directed endoradiotherapy","volume":"184","author":"Lapa","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Komek, H., Gundogan, C., and Can, C. (2020). 68Ga-FAPI PET\/CT Versus 68Ga-DOTATATE PET\/CT in the Evaluation of a Patient With Neuroendocrine Tumor. Clin. Nucl. Med.","DOI":"10.1097\/RLU.0000000000003490"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:04Z","timestamp":1760362384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/4\/605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,29]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["diagnostics11040605"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11040605","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,29]]}}}