Viktoria E Krol, Aditya Bansal, Manasa Kethamreddy, Jason R Ellinghuysen, Daniel J Vail, Fabrice Lucien-Matteoni, Haidong Dong, Sean S Park, Mukesh K Pandey
{"title":"钪-44放射性标记纳米体作为PD-L1 PET成像探针的合成及体外评价。","authors":"Viktoria E Krol, Aditya Bansal, Manasa Kethamreddy, Jason R Ellinghuysen, Daniel J Vail, Fabrice Lucien-Matteoni, Haidong Dong, Sean S Park, Mukesh K Pandey","doi":"10.3390/pharmaceutics17060796","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objective</b>: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with <sup>44</sup>Sc (t<sub>1/2</sub> = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as <sup>89</sup>Zr (t<sub>1/2</sub> = 78.41 h). <b>Methods</b>: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with <sup>44</sup>Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (<i>n</i> = 3) for [<sup>44</sup>Sc]Sc-B11-IgG and 73.6 ± 12.1% (<i>n</i> = 3) for [<sup>44</sup>Sc]Sc-B11-nanobody, before purification. <b>Results</b>: Significantly higher uptake in the PD-L1<sub>+</sub> cells than PD-L1<sub>KO</sub> cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. <b>Conclusions</b>: Due to the high non-specific uptake in vitro, the <sup>44</sup>Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with <sup>44</sup>Sc, due to their well-matched biological and physical half-life.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 6","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196724/pdf/","citationCount":"0","resultStr":"{\"title\":\"Synthesis and In Vitro Evaluation of a Scandium-44 Radiolabeled Nanobody as a PD-L1 PET Imaging Probe.\",\"authors\":\"Viktoria E Krol, Aditya Bansal, Manasa Kethamreddy, Jason R Ellinghuysen, Daniel J Vail, Fabrice Lucien-Matteoni, Haidong Dong, Sean S Park, Mukesh K Pandey\",\"doi\":\"10.3390/pharmaceutics17060796\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background/Objective</b>: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with <sup>44</sup>Sc (t<sub>1/2</sub> = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as <sup>89</sup>Zr (t<sub>1/2</sub> = 78.41 h). <b>Methods</b>: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with <sup>44</sup>Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (<i>n</i> = 3) for [<sup>44</sup>Sc]Sc-B11-IgG and 73.6 ± 12.1% (<i>n</i> = 3) for [<sup>44</sup>Sc]Sc-B11-nanobody, before purification. <b>Results</b>: Significantly higher uptake in the PD-L1<sub>+</sub> cells than PD-L1<sub>KO</sub> cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. <b>Conclusions</b>: Due to the high non-specific uptake in vitro, the <sup>44</sup>Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with <sup>44</sup>Sc, due to their well-matched biological and physical half-life.</p>\",\"PeriodicalId\":19894,\"journal\":{\"name\":\"Pharmaceutics\",\"volume\":\"17 6\",\"pages\":\"\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196724/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/pharmaceutics17060796\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/pharmaceutics17060796","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Synthesis and In Vitro Evaluation of a Scandium-44 Radiolabeled Nanobody as a PD-L1 PET Imaging Probe.
Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.
PharmaceuticsPharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍:
Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.