Synthesis and In Vitro Evaluation of a Scandium-44 Radiolabeled Nanobody as a PD-L1 PET Imaging Probe
<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, radi...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/6/796 |
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| Summary: | <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. |
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| ISSN: | 1999-4923 |