PET Imaging of Integrin αVβ3 Expression

Abstract

PET imaging of integrin αvβ3 expression has been studied intensely by the academia and recently also by the industry. Imaging of integrin αvβ3 expression is of great potential value, as the integrin αvβ3 is a key player in tumor metastasis and angiogenesis. Therefore PET imaging of this target might be a suitable in-vivo biomarker of angiogenesis and metastatic potential of tumors. In this manuscript, the various strategies for PET imaging of the integrin αvβ3 will be summarized, including monomeric and multimeric radiolabelled RGD peptides and nanoparticles. While most experiments have been performed using preclinical tumor models, more and more clinical results on PET imaging of αvβ3 expression are available and will be discussed in detail. However, while a multitude of radiotracer strategies have been successfully evaluated for PET imaging of αvβ3, the ultimate clinical value of this new imaging biomarker still has to be evaluated in large clinical trials.

Keywords: PET; angiogenesis; integrin αvβ3; metastasis; molecular imaging.

Figure 1

Example of a [¹⁸F]Galacto-RGD microPET scan of a nude mouse (A) with a Lewis Lung Cell Cancer (LLC) and a M21 melanoma xenograft (M21). Corresponding immunohistochemistry of αvβ3 expression is shown for the LLC in B and for the M21 tumour in C. The LLC tumor shows αvβ3 expression on the neovasculature but not on the tumor cells, while the M21 tumour shows αvβ3 expression both on the neovasculature and on the tumor cells. Consequently, the PET signal is much more intense in the M21 tumour and only moderate in the LLC tumor.

Figure 2

Two patients with sarcomas of the thigh (arrows). On the left side a patient with osteosarcoma of the right femur (A, B), on the right side a patient with a liposarcoma (C, D). In the MRI (A, C: T1w contrast enhanced, with fat suppression; transaxial) you see the large tumors with intense contrast enhancement. Despite the similar patterns of contrast enhancement, the corresponding [¹⁸F]Galacto-RGD PET (B, D transaxial slices) shows quite different uptake patterns in both patients: in the osteosarcoma we see intense tracer uptake, predominantly in the tumor periphery, whereas in the liposarcoma there is mostly faint tracer uptake, with some focal areas of more intense tracer uptake. This suggests very heterogeneous αvβ3 expression in these two tumors, despite intense contrast enhancement of both lesions.

Figure 3

Example of multimodality multiparametric imaging of tumor biology in a patient with a metastasis of lung cancer to the right acetabulum (arrows). The [¹⁸F]FDG PET/CT (A: PET; B: PET/CT) shows intense tracer uptake in the lesion. [¹⁸F]Galacto-RGD PET (C: PET; D: PET/MRI image fusion) also shows intense tracer uptake, suggesting elevated αvβ3 expression in the lesion. Diffusion weighted MRI (E: b600 image, F: ADC map) shows restricted water diffusivity in the lesion as a potential marker of tumor cellularity. Finally DCE-MRI (G: subtraction image; H: contrast-enhanced T1w image) shows intense contrast enhancement of the lesion.