{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:19:33Z","timestamp":1792887573729,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH","award":["R01 CA248493"],"award-info":[{"award-number":["R01 CA248493"]}]},{"name":"NIH","award":["P50 CA094056"],"award-info":[{"award-number":["P50 CA094056"]}]},{"name":"NIH","award":["P30 CA091842"],"award-info":[{"award-number":["P30 CA091842"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Multiple myeloma (MM) affects over 35,000 patients each year in the US. There remains a need for versatile Positron Emission Tomography (PET) tracers for the detection, accurate staging, and monitoring of treatment response of MM that have optimal specificity and translational attributes. CD38 is uniformly overexpressed in MM and thus represents an ideal target to develop CD38-targeted small molecule PET radiopharmaceuticals to address these challenges.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Procedures<\/jats:title>\n                <jats:p>Using phage display peptide libraries and pioneering algorithms, we identified novel CD38 specific peptides. Imaging bioconjugates were synthesized using solid phase peptide chemistry, and systematically analyzed <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> in relevant MM systems.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The CD38-targeted\u00a0bioconjugates were radiolabeled with copper-64 (<jats:sup>64<\/jats:sup>Cu) with100% radiochemical purity and an average specific activity of 3.3 \u2013 6.6\u00a0MBq\/nmol. The analog NODAGA-PEG4-SL022-GGS (SL022: Thr-His-Tyr-Pro-Ile-Val-Ile) had a K<jats:sub>d<\/jats:sub> of 7.55\u2009\u00b1\u20090.291\u00a0nM and was chosen as the lead candidate. <jats:sup>64<\/jats:sup>Cu-NODAGA-PEG4-SL022-GGS demonstrated high binding affinity to CD38 expressing human myeloma MM.1S-CBR-GFP-WT cells, which was blocked by the non-radiolabeled version of the peptide analog and anti-CD38 clinical antibodies, daratumumab and isatuximab, by 58%, 73%, and 78%, respectively. The CD38 positive MM.1S-CBR-GFP-WT cells had\u2009&gt;\u200968% enhanced cellular binding when compared to MM.1S-CBR-GFP-KO cells devoid of CD38. Furthermore, our new CD38-targeted radiopharmaceutical allowed visualization of tumors located in marrow rich bones, remaining there for up to 4\u00a0h. Clearance from non-target organs occurred within 60\u00a0min. Quantitative PET data from a murine disseminated tumor model showed significantly higher accumulation in the bones of tumor-bearing animals compared to tumor-na\u00efve animals (SUV<jats:sub>max<\/jats:sub> 2.06\u2009\u00b1\u20090.4 versus 1.24\u2009\u00b1\u20090.4, P\u2009=\u20090.02). Independently, tumor uptake of the target compound was significantly higher (P\u2009=\u20090.003) compared to the scrambled peptide, <jats:sup>64<\/jats:sup>Cu-NODAGA-PEG4-SL041-GGS (SL041: Thr-Tyr-His-Ile-Pro-Ile-Val). The subcutaneous MM model demonstrated significantly higher accumulation in tumors compared to muscle at 1 and 4\u00a0h after tracer administration (SUV<jats:sub>max<\/jats:sub> 0.8\u2009\u00b1\u20090.2 and 0.14\u2009\u00b1\u20090.04, P\u2009=\u20090.04 at 1\u00a0h; SUV<jats:sub>max<\/jats:sub> 0.89\u2009\u00b1\u20090.01 and 0.09\u2009\u00b1\u20090.01, P\u2009=\u20090.0002 at 4\u00a0h).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The novel CD38-targeted, radiolabeled bioconjugates were specific and allowed visualization of MM, providing a starting point for the clinical translation of such tracers for the detection of MM.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11307-024-01901-5","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T20:40:20Z","timestamp":1710362420000},"page":"738-752","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Development of New CD38 Targeted Peptides for Cancer Imaging"],"prefix":"10.1007","volume":"26","author":[{"given":"Alexander","family":"Zheleznyak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Manion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baogang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Vanover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchal","family":"Ghai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Prior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Lees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Achilefu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8114-9584","authenticated-orcid":false,"given":"Monica","family":"Shokeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"1901_CR1","doi-asserted-by":"crossref","unstructured":"Szlasa W, Czarny J, Sauer N et al (2022) Targeting CD38 in neoplasms and non-cancer diseases. 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