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Engineered antibody fragments for immuno-PET imaging of endogenous CD8+ T cells in vivo.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 1/21/2014, Vol. 111 Issue 3, p1108-1113, 6p
- Publication Year :
- 2014
-
Abstract
- The noninvasive detection and quantification of CD8<superscript>+</superscript> T cells in vivo are important for both the detection and staging of CD8<superscript>+</superscript> lymphomas and for the monitoring of successful cancer immunotherapies, such as adoptive cell transfer and antibody-based immunotherapeutics. Here, antibody fragments are constructed to target murine CD8 to obtain rapid, high-contrast immuno-positron emission tomography (immuno-PET) images for the detection of CD8 expression in vivo. The variable regions of two anti-murine CD8-depleting antibodies (clones 2.43 and YTS169.4.2.1) were sequenced and reformatted into minibody (Mb) fragments (scFv-C<subscript>H</subscript>3). After production and purification, the Mbs retained their antigen specificity and bound primary CD8<superscript>+</superscript> T cells from the thymus, spleen, lymph nodes, and peripheral blood. Importantly, engineering of the parental antibodies into Mbs abolished the ability to deplete CD8<superscript>+</superscript> T cells in vivo. The Mbs were subsequently conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid for <superscript>64</superscript>Cu radiolabeling. The radiotracers were injected i.v. into antigen-positive, antigen-negative, immunodeficient, antigen-blocked, and antigen-depleted mice to evaluate specificity of uptake in lymphoid tissues by immuno-PET imaging and ex vivo biodistribution. Both <superscript>64</superscript>Cu-radiolabeled Mbs produced high-contrast immuno-PET images 4 h postinjection and showed specific uptake in the spleen and lymph nodes of antigen-positive mice. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 111
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 93919804
- Full Text :
- https://doi.org/10.1073/pnas.1316922111