ImmunoPET Imaging of CD47 with VHH-Derived Tracers in Pancreatic Cancers

• DOI: 10.1021/acs.molpharmaceut.3c00311
• Publication Date: 2023-07-05T12:01:04Z
• Authors: Chenyi Liang; Wei Huang; You Zhang; Di Zhang; Shuxian An; Qianyun Wu; Haitao Zhao; Cheng Wang; Gang Huang; Weijun Wei; Jianjun Liu
• Keywords: CD47; Biodistribution

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with insidious onset, rapid progression, and very poor prognosis. CD47 transmembrane protein associated the development prognosis of pancreatic cancer. The aim this study was to evaluate diagnostic value novel immunoPET tracers targeting in preclinical cancer models. association expression analyzed using Gene Expression Profiling Interactive Analysis platform. Immunohistochemical analysis tissue microarrays performed detect PDAC. levels on BxPC-3 AsPC-1 cell membranes were compared flow cytometry. A VHH (C2)-targeting human its albumin-binding derivative (ABDC2) labeled 68Ga or 89Zr, respectively. developed evaluated by immuno-positron emission tomography (immunoPET) imaging tumor-bearing nude CD47-humanized mice. [68Ga]Ga-NOTA-C2 effectively detected lesions mice models further showed confirmative capacity PDAC Compared [68Ga]Ga-NOTA-C2, [89Zr]Zr-DFO-ABDC2 had significantly prolonged circulation time, increased uptake, reduced accumulation kidneys. Finally, biodistribution histological staining confirmed results studies. In study, we validated that two VHH-derived molecular for ([68Ga]Ga-NOTA-C2 [89Zr]Zr-DFO-ABDC2) can annotate diagnose target-specific manner. Clinical application strategies may help select patients CD47-targeted therapies assess response thereafter.