Development of an 18 F-labeled anti-human CD8 VHH for same-day immunoPET imaging.
(2023) Eur J Nucl Med Mol Imaging 50: 679-691
Authors: Sriraman, S.K., Davies, C.W., Gill, H., Kiefer, J.R., Yin, J., Ogasawara, A., Urrutia, A., Javinal, V., Lin, Z., Seshasayee, D., Abraham, R., Haas, P., Koth, C., Marik, J., Koerber, J.T., Williams, S.P.
Abstract
Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8 + T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8 + cells could provide a critical biomarker for new CIT agents. However, existing 89 Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging. To this end, we discovered and developed a 13-kDa single-domain antibody (VHH5v2) against human CD8 to enable high-quality, same-day imaging with a reduced radiation burden. To enable sensitive and rapid imaging, we employed a site-specific conjugation strategy to introduce an 18 F radiolabel to the VHH. The anti-CD8 VHH, VHH5v2, demonstrated binding to a membrane distal epitope of human CD8 with a binding affinity (K D ) of 500 pM. Subsequent imaging experiments in several xenografts that express varying levels of CD8 demonstrated rapid tumor uptake and fast clearance from the blood. High-quality images were obtained within 1 h post-injection and could quantitatively differentiate the tumor models based on CD8 expression level. Our work reveals the potential of this anti-human CD8 VHH [ 18 F]F-VHH5v2 to enable rapid and specific imaging of CD8 + cells in the clinic.
Development of an 18 F-labeled anti-human CD8 VHH for same-day immunoPET imaging.
(2023) Eur J Nucl Med Mol Imaging 50: 679-691
Authors: Sriraman, S.K., Davies, C.W., Gill, H., Kiefer, J.R., Yin, J., Ogasawara, A., Urrutia, A., Javinal, V., Lin, Z., Seshasayee, D., Abraham, R., Haas, P., Koth, C., Marik, J., Koerber, J.T., Williams, S.P.
Abstract
Cancer immunotherapies (CITs) have revolutionized the treatment of certain cancers, but many patients fail to respond or relapse from current therapies, prompting the need for new CIT agents. CD8 + T cells play a central role in the activity of many CITs, and thus, the rapid imaging of CD8 + cells could provide a critical biomarker for new CIT agents. However, existing 89 Zr-labeled CD8 PET imaging reagents exhibit a long circulatory half-life and high radiation burden that limit potential applications such as same-day and longitudinal imaging. To this end, we discovered and developed a 13-kDa single-domain antibody (VHH5v2) against human CD8 to enable high-quality, same-day imaging with a reduced radiation burden. To enable sensitive and rapid imaging, we employed a site-specific conjugation strategy to introduce an 18 F radiolabel to the VHH. The anti-CD8 VHH, VHH5v2, demonstrated binding to a membrane distal epitope of human CD8 with a binding affinity (K D ) of 500 pM. Subsequent imaging experiments in several xenografts that express varying levels of CD8 demonstrated rapid tumor uptake and fast clearance from the blood. High-quality images were obtained within 1 h post-injection and could quantitatively differentiate the tumor models based on CD8 expression level. Our work reveals the potential of this anti-human CD8 VHH [ 18 F]F-VHH5v2 to enable rapid and specific imaging of CD8 + cells in the clinic.
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