{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:05:08Z","timestamp":1789963508723,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018985","name":"Waalse Gewest","doi-asserted-by":"publisher","award":["2310145"],"award-info":[{"award-number":["2310145"]}],"id":[{"id":"10.13039\/100018985","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004973","name":"Barndiabetesfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008550","name":"Diabetesfonden","doi-asserted-by":"publisher","award":["2020\u201002312"],"award-info":[{"award-number":["2020\u201002312"]}],"id":[{"id":"10.13039\/501100008550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008550","name":"Diabetesfonden","doi-asserted-by":"publisher","award":["2024\u201003659"],"award-info":[{"award-number":["2024\u201003659"]}],"id":[{"id":"10.13039\/501100008550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["24\u00a03754\u00a0Pj"],"award-info":[{"award-number":["24\u00a03754\u00a0Pj"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["24\u00a03889\u00a0Pj"],"award-info":[{"award-number":["24\u00a03889\u00a0Pj"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001648","name":"European Foundation for the Study of Diabetes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Dipeptidyl peptidase\u2010like protein 6 (DPP6) is a potential molecular imaging biomarker for pancreatic and transplanted islets of Langerhans. 4hD29 is a single\u2010domain antibody with nanomolar affinity for DPP6. Here, we demonstrate the generation and validation of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga\u2010NOTA\u20104hD29 for Positron Emission Tomography (PET) imaging of human stem cell\u2010derived islets (SC\u2010islets) and human islets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The binding of fluorescently labelled 4hD29 to human islets, human beta cell models and pancreatic tissues from various species over time was characterised. NOTA\u20104hD29 was radiolabelled with Gallium\u201068, and the resulting tracer [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga\u2010NOTA\u20104hD29 was evaluated for in\u00a0vitro DPP6 binding as well as in\u00a0vivo biodistribution. In\u00a0vivo PET imaging was performed in immunodeficient mice transplanted with 400 to 800 SC\u2010islets or human islets, and the uptake signal was compared to non\u2010transplanted control mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fluorescently labelled 4hD29 demonstrated specific binding and internalisation in human islets. Fluorescence signal remained detectable for up to 2\u2009h following incubation, indicating sustained intracellular retention. [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga\u2010NOTA\u20104hD29 bound to human islets with high specificity, and binding intensity correlated to islet purity. The binding of fluorescent and radiolabelled 4hD29 was negligible in extra\u2010pancreatic tissues. In\u00a0vivo PET imaging enabled reliable detection of grafts comprised of 400 to 800 SC\u2010islets or human islets in immunodeficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga\u2010NOTA\u20104hD29 is a promising PET tracer for in\u00a0vivo imaging of DPP6 in human islets. The tracer enabled non\u2010invasive detection of transplanted human islet grafts in the 400\u2013800 IEQ range and demonstrated favourable biodistribution and dosimetry profiles, supporting its further development for islet imaging applications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71343","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:34:07Z","timestamp":1789961647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <scp>DPP6<\/scp>\n                    \u2010Targeted\n                    <scp>PET<\/scp>\n                    Tracer for Non\u2010Invasive Imaging of Transplanted Human Islets"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8567-2277","authenticated-orcid":false,"given":"Amina","family":"Khalil","sequence":"first","affiliation":[{"name":"Science for Life Laboratory, Department of Medicinal Chemistry Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Roca\u2010Rivada","sequence":"additional","affiliation":[{"name":"ULB Center for Diabetes Research, Medical Faculty Universit\u00e9 Libre De Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svitlana","family":"Vasylovska","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo J. I.","family":"Balestri","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Velikyan","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medicinal Chemistry Uppsala University  Uppsala Sweden"},{"name":"PET Center Uppsala University Hospital  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayro","family":"Jawurek","sequence":"additional","affiliation":[{"name":"ULB Center for Diabetes Research, Medical Faculty Universit\u00e9 Libre De Bruxelles  Brussels Belgium"},{"name":"InSphero AG  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra C.","family":"Title","sequence":"additional","affiliation":[{"name":"InSphero AG  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcak","family":"Yesildag","sequence":"additional","affiliation":[{"name":"InSphero AG  Schlieren Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke R.","family":"Odell","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decio L.","family":"Eizirik","sequence":"additional","affiliation":[{"name":"ULB Center for Diabetes Research, Medical Faculty Universit\u00e9 Libre De Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-8790","authenticated-orcid":false,"given":"Olof","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medicinal Chemistry Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00125-019-4822-4","article-title":"Beta Cells in Type 1 Diabetes: Mass and Function; Sleeping or Dead?","volume":"62","author":"Oram R. 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