Gallium-68-labeled affibody molecule for PET imaging of PDGFRß expression in vivo.

Platelet-derived growth factor receptor ß (PDGFRß) is a transmembrane tyrosine kinase receptor involved, for example, in angiogenesis. Overexpression and excessive signaling of PDGFRß has been observed in multiple malignant tumors and fibrotic diseases, making this receptor a pharmaceutical target for monoclonal antibodies and tyrosine kinase inhibitors. Successful targeted therapy requires identification of responding patients. Radionuclide molecular imaging would enable determination of the PDGFRß status in all lesions using a single noninvasive repeatable procedure. Recently, we have demonstrated that the affibody molecule Z09591 labeled with (111)In can specifically target PDGFRß-expressing tumors in vivo. The use of positron emission tomography (PET) as an imaging technique would provide superior resolution, sensitivity, and quantitation accuracy. In this study, a DOTA-conjugated Z09591 was labeled with the generator-produced positron emitting radionuclide (68)Ga (T1/2 = 67.6 min, Eß + max = 1899 keV, 89% ß(+)). (68)Ga-DOTA-Z09591 retained the capacity to specifically bind to PDGFRß-expressing U-87 MG glioma cells. The half-maximum inhibition concentration (IC50) of (68)Ga-DOTA-Z09591 (6.6 ± 1.4 nM) was somewhat higher than that of (111)In-DOTA-Z09591 (1.4 ± 1.2 nM). (68)Ga-DOTA-Z09591 demonstrated specific (saturable) targeting of U-87 MG xenografts in immunodeficient mice. The tumor uptake at 2 h after injection was 3.7 ± 1.7% IA/g, which provided a tumor-to-blood ratio of 8.0 ± 3.1. The only organ with higher accumulation of radioactivity was the kidney. MicroPET imaging provided high-contrast imaging of U-87 MG xenografts. In conclusion, the (68)Ga-labeled affibody molecule Z09591 is a promising candidate for further development as a probe for imaging PDGFRß expression in vivo using PET.