{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:24:55Z","timestamp":1790504695799,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010535","name":"Actinium Pharmaceuticals","doi-asserted-by":"publisher","award":["419625"],"award-info":[{"award-number":["419625"]}],"id":[{"id":"10.13039\/100010535","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Objective: Positron emission tomography (PET) imaging is a powerful non-invasive method to determine the in vivo behavior of biomolecules. Determining biodistribution and pharmacokinetic (PK) properties of targeted therapeutics can enable a better understanding of in vivo drug mechanisms such as tumor uptake, off target accumulation and clearance. Zirconium-89 (89Zr) is a readily available tetravalent PET-enabling radiometal that has been used to evaluate the biodistribution and PK of monoclonal antibodies. In the current study, we performed in vitro and in vivo characterization of 89Zr-lintuzumab, a radiolabeled anti-CD33 antibody, as a model to evaluate the in vivo binding properties in preclinical models of AML. Methods: Lintuzumab was conjugated to p-SCN-Bn-deferoxamine (DFO) and labeled with 89Zr using a 5:1 \u00b5Ci:\u00b5g specific activity at 37 \u00b0C for 1h. The biological activity of 89Zr-lintuzumab was evaluated in a panel of CD33 positive cells using flow cytometry. Fox Chase SCID mice were injected with 2 \u00d7 106 OCI-AML3 cells into the right flank. After 12 days, a cohort of mice (n = 4) were injected with 89Zr-lintuzumab via tail vein. PET\/CT scans of mice were acquired on days 1, 2, 3 and 7 post 89Zr-lintuzumab injection. To demonstrate 89Zr-lintuzumab specific binding to CD33 expressing tumors in vivo, a blocking study was performed. This cohort of mice (n = 4) was injected with native lintuzumab and 24 h later 89Zr-lintuzumab was administered. This group was imaged 3 and 7 days after injection of 89Zr-lintuzumab. A full ex vivo biodistribution study on both cohorts was performed on day 7. The results from the PET image and ex vivo biodistribution studies were compared. Results: Lintuzumab was successfully radiolabeled with 89Zr resulting in a 99% radiochemical yield. The 89Zr-lintuzumab radioconjugate specifically binds CD33 positive cells in a similar manner to native lintuzumab as observed by flow cytometry. PET imaging revealed high accumulation of 89Zr-lintuzumab in OCI-AML3 tumors within 24h post-injection of the radioconjugate. The 89Zr-lintuzumab high tumor uptake remains for up to 7 days. Tumor analysis of the PET data using volume of interest (VOI) showed significant blocking of 89Zr-lintuzumab in the group pre-treated with native lintuzumab (pre-blocked group), thus indicating specific targeting of CD33 on OCI-AML3 cells in vivo. The tumor uptake findings from the PET imaging study are in agreement with those from the ex vivo biodistribution results. Conclusions: PET imaging of 89Zr-lintuzumab shows high specific uptake in CD33 positive human OCI-AML3 tumors. The results from the image study agree with the observations from the ex vivo biodistribution study. Our findings collectively suggest that PET imaging using 89Zr-lintuzumab could be a powerful drug development tool to evaluate binding properties of anti-CD33 monoclonal antibodies in preclinical cancer models.<\/jats:p>","DOI":"10.3390\/molecules27196589","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"6589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Vitro and In Vivo Characterization of 89Zirconium-Labeled Lintuzumab Molecule"],"prefix":"10.3390","volume":"27","author":[{"given":"Kevin J. H.","family":"Allen","sequence":"first","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin","family":"Jiao","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Li","sequence":"additional","affiliation":[{"name":"Actinium Pharmaceuticals, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis R.","family":"Beckford-Vera","sequence":"additional","affiliation":[{"name":"Actinium Pharmaceuticals, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Dadachova","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41571-022-00652-y","article-title":"Radiotheranostics in oncology: Current challenges and emerging opportunities","volume":"19","author":"Bodei","year":"2022","journal-title":"Nat. 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