Gallium-68-Labeled Z_PDGFRβ Affibody: A Potential PET Probe for Platelet-Derived Growth Factor Receptor β-Expressing Carcinomas

Abstract

Platelet-derived growth factor receptor β (PDGFRβ) has been demonstrated to be an effective biomarker for a variety of malignant cancers, and affibody-based PDGFRβ molecules have potential as positron emission tomography (PET) tracers for the diagnosis of cancers. Based on previous pharmacokinetics studies, short-lived positron emission radionuclides, such as fluorine-18 and gallium-68, would be more suitable for affibody-based PET imaging. Thus, in the present study, we prepared a gallium-68-labeled PDGFRβ-targeting dimeric affibody conjugate and evaluated its capability for visualizing malignant tumors by micro-PET/computed tomography (CT) imaging. The PDGFRβ-targeting Z PDGFRβ affibody was conjugated with the p-NCS-Bn-DOTA macrocyclic ligand and radiolabeled with gallium-68 to generate the 68 Ga-DOTA-Z PDGFRβ PET probe . Then, several types of malignant carcinoma cells (U-87 MG, LS 174T, A549, H1688, and H446) were used to evaluate the targeted cellular binding capability of the PET probe through in vitro/in vivo cellular assays and whole-body imaging by micro-PET/CT. The 68 Ga-DOTA-Z PDGFRβ was successfully prepared with a radiochemical yield of 93% and exhibited ideal stability for up to 4 h at room temperature in vitro. This radioactive conjugate demonstrated specific binding ability with PDGFRβ-expressing U-87 MG cells, which was suppressed by PDGFRβ ligands. The biodistribution of 68 Ga-DOTA-Z PDGFRβ indicated fast liver clearance and a kidney-bladder excretion route. The U-87 MG xenografted tumor was clearly visualized with 68 Ga-DOTA-Z PDGFRβ at 1 h postinjection using micro-PET/CT imaging. 68 Ga-DOTA-Z PDGFRβ is a potential radiopharmaceutical for the diagnosis of PDGFRβexpressing tumors.

Synthesis and Evaluation of [18F]SiFA-Conjugated Ligands for Fibroblast Activation Protein Imaging

“…Radioligand [ 18 F]2 was selected for the cell binding study because of its favorable partition coefficient compared to that of [ 18 F]1 and was evaluated in vitro with and without FAPI-04 using U87MG cells expressing FAP. 38 The results confirmed that the cell binding of [ 18 F]2 was FAP-specific (Figure 2B).…”