Knight JC

Leslie J

Luli S

Oakley F

Pringle TA

Ramon-Gil E

Wright MC

English

Synaptophysin is expressed on fibrogenic hepatic myofibroblasts. C1-3 is a single chain human antibody (scAb) that binds specifically to synaptophysin on hepatic myofibroblasts, providing a targeting vector for novel in vivo imaging agents of chronic liver disease. C1-3 and a negative control scAb, CSBD9, were radiolabelled with zirconium-89 via desferrioxamine chelation to enable non-invasive molecular imaging with Positron Emission Tomography (PET). DFO-scAb conjugates were characterised by gel electrophoresis (SDS-PAGE) and MALDI-TOF spectrometry, and 89Zr-labelled with high radiolabelling efficiency (99%). [89Zr]Zr-DFO-C1-3 exhibited high in vitro stability (&gt;99%) in mouse and human sera over three days at 25 and 37\ub0C. Activated hepatic myofibroblasts incubated with [89Zr]Zr-DFO-C1-3 displayed significantly higher internalised activity (59.46%, P = 0.001) compared to the [89Zr]Zr-DFO-CSBD9 control, indicating synaptophysin-mediated uptake and high binding specificity of [89Zr]Zr-DFO-C1-3. Mice with CCl4-induced acute liver damage exhibited significantly higher liver uptake of [89Zr]Zr-DFO-C1-3, compared to controls, confirmed by both Cerenkov imaging and ex vivo gamma counting (4.41 \ub1 0.19 %ID/g, P &lt; 0.0001). CCl4-induced liver damage and the number of hepatic myofibroblasts was confirmed by aSMA staining of liver sections. These findings indicate that [89Zr]Zr-DFO-C1-3 has promising utility as a PET imaging agent for non-invasive detection of hepatic myfibroblasts following acute liver injury

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Synthesis and Preclinical Evaluation of a <sup>89</sup>Zr-labelled Human Single Chain Antibody for Non-invasive Detection of Hepatic Myofibroblasts in Acute Liver Injury

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Synthesis and Preclinical Evaluation of a <sup>89</sup>Zr-labelled Human Single Chain Antibody for Non-invasive Detection of Hepatic Myofibroblasts in Acute Liver Injury

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