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Although EphA2 is considered a promising target receptor for theranostic applications, suitable radiotracers for clinical imaging have been lacking. This study reports first clinical experiences with [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-BCY18469, a bicyclic peptide radiotracer for EphA2-targeted PET imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seven patients with histologically confirmed PDAC (5 after chemotherapy, 2 at initial staging) underwent PET\/CT imaging. Four were scanned at 15, 30, 45, 60 and 180\u00a0min. and three at 45\u00a0min. after injection of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-BCY18469. Dosimetry calculations were performed based on organ-specific time-activity curves from whole-body PET acquisitions. Imaging findings were compared with contrast-enhanced CT or MRI (interval: 9\u201350 days).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No adverse events were observed. The kidneys received the highest absorbed dose (0.31\u2009\u00b1\u20090.02 mGy\/MBq), while the effective dose was 0.017\u2009\u00b1\u20090.002 mSv\/MBq. [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-BCY18469 demonstrated rapid tumor uptake at 15\u00a0min. post-injection with predominantly renal excretion. Of 45 total lesions EphA2-PET detected 36 lesions with tracer uptake suspicious for metastasis. 11 of 45 lesions were detected only on EphA2-PET, whereas 9 of 45 lesions were detected only on CT and\/or MRI. The tracer identified 13 liver metastases (SUV\n                      <jats:sub>max<\/jats:sub>\n                      6.9\u2009\u00b1\u20093.4) and 13 lymph node metastases (SUV\n                      <jats:sub>max<\/jats:sub>\n                      5.0\u2009\u00b1\u20091.1), among other findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our initial clinical experiences demonstrate that [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-BCY18469 enables safe, rapid, and high-contrast visualization of EphA2-expressing PDAC lesions. These results strongly support further investigation of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-BCY18469 as a diagnostic tool for EphA2-positive malignancies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-07985-1","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:38:40Z","timestamp":1781077120000},"page":"6363-6374","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First-in-human EphA2-targeting PET imaging with the bicyclic radiotracer [68Ga]Ga-BCY18469 in pancreatic cancer patients: biodistribution, dosimetry and initial findings"],"prefix":"10.1007","volume":"53","author":[{"given":"Ann-Christin","family":"Eder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph-Ferdinand","family":"Wielenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Aymen","family":"Omrane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Klotsotyra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Fakiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Quante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Eder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp T.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-6873","authenticated-orcid":false,"given":"Martin T.","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"7985_CR1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","volume":"133","author":"EB Pasquale","year":"2008","unstructured":"Pasquale EB. 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The radiopharmaceutical was administered under \u00a7\u00a013(2b) of the German Medicinal Products Act (Arzneimittelgesetz, AMG) permitting individualized radiopharmaceutical preparation for selected patients.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have reviewed and approved the final version of the manuscript for submission and publication.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients received comprehensive information regarding the investigational nature of this imaging procedure and provided written informed consent prior to participation.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DKFZ Heidelberg\/DKTK Freiburg received funding from Bicycle Therapeutics for joint preclinical projects. For the clinical work performed at University Hospital Freiburg, only BCY18469 precursor was provided by Bicycle Therapeutics with no additional funding. The authors declare that artificial intelligence (AI) tools were used in the preparation of this manuscript. Specifically, AI-based software was utilized for language assistance during the drafting and editing phases. The use of AI was conducted in accordance with ethical guidelines, and all results were independently verified by the authors to ensure accuracy and integrity.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}