Gallium-68-Labeled Z(PDGFR beta) Affibody: A Potential PET Probe for Platelet-Derived Growth Factor Receptor beta-Expressing Carcinomas

Platelet-derived growth factor receptor beta (PDGFR beta) has been demonstrated to be an effective biomarker for a variety of malignant cancers, and affibody-based PDGFR beta 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 PDGFR beta-targeting dimeric affibody conjugate and evaluated its capability for visualizing malignant tumors by micro-PET/computed tomography (CT) imaging. The PDGFR beta-targeting Z(PDGFR beta) affibody was conjugated with the p-NCS-Bn-DOTA macrocyclic ligand and radiolabeled with gallium-68 to generate the Ga-68-DOTA-Z(PDGFR beta) 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 Ga-68-DOTA-Z(PDGFR beta) 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 PDGFR beta-expressing U-87 MG cells, which was suppressed by PDGFRfl ligands. The biodistribution of Ga-68-DOTA-Z(PDGFR beta) indicated fast liver clearance and a kidney-bladder excretion route. The U-87 MG xenografted tumor was clearly visualized with Ga-68-DOTA-Z(PDGFR beta) at 1 h postinjection using micro-PET/CT imaging. Ga-68-DOTA-Z(PDGFR beta) is a potential radiopharmaceutical for the diagnosis of PDGFR beta-expressing tumors.